text:
1. In the twelfth year of Ahaz king of Judah began Hoshea the son of Elah to reign in Samaria over Israel nine years.
2. And he did that which was evil in the sight of the LORD, but not as the kings of Israel that were before him.
3. Against him came up Shalmaneser king of Assyria; and Hoshea became his servant, and gave him presents.
4. And the king of Assyria found conspiracy in Hoshea: for he had sent messengers to So king of Egypt, and brought no present to the king of Assyria, as he had done year by year: therefore the king of Assyria shut him up, and bound him in prison.
5. Then the king of Assyria came up throughout all the land, and went up to Samaria, and besieged it three years.
6. In the ninth year of Hoshea the king of Assyria took Samaria, and carried Israel away into Assyria, and placed them in Halah and in Habor by the river of Gozan, and in the cities of the Medes.
7. For so it was, that the children of Israel had sinned against the LORD their God, which had brought them up out of the land of Egypt, from under the hand of Pharaoh king of Egypt, and had feared other gods,
8. And walked in the statutes of the heathen, whom the LORD cast out from before the children of Israel, and of the kings of Israel, which they had made.
9. And the children of Israel did secretly those things that were not right against the LORD their God, and they built them high places in all their cities, from the tower of the watchmen to the fenced city.
10. And they set them up images and groves in every high hill, and under every green tree:
11. And there they burnt incense in all the high places, as did the heathen whom the LORD carried away before them; and wrought wicked things to provoke the LORD to anger:
12. For they served idols, whereof the LORD had said unto them, Ye shall not do this thing.
13. Yet the LORD testified against Israel, and against Judah, by all the prophets, and by all the seers, saying, Turn ye from your evil ways, and keep my commandments and my statutes, according to all the law which I commanded your fathers, and which I sent to you by my servants the prophets.
14. Notwithstanding they would not hear, but hardened their necks, like to the neck of their fathers, that did not believe in the LORD their God.
15. And they rejected his statutes, and his covenant that he made with their fathers, and his testimonies which he testified against them; and they followed vanity, and became vain, and went after the heathen that were round about them, concerning whom the LORD had charged them, that they should not do like them.
16. And they left all the commandments of the LORD their God, and made them molten images, even two calves, and made a grove, and worshipped all the host of heaven, and served Baal.
17. And they caused their sons and their daughters to pass through the fire, and used divination and enchantments, and sold themselves to do evil in the sight of the LORD, to provoke him to anger.
18. Therefore the LORD was very angry with Israel, and removed them out of his sight: there was none left but the tribe of Judah only.
19. Also Judah kept not the commandments of the LORD their God, but walked in the statutes of Israel which they made.
20. And the LORD rejected all the seed of Israel, and afflicted them, and delivered them into the hand of spoilers, until he had cast them out of his sight.
21. For he rent Israel from the house of David; and they made Jeroboam the son of Nebat king: and Jeroboam drave Israel from following the LORD, and made them sin a great sin.
22. For the children of Israel walked in all the sins of Jeroboam which he did; they departed not from them;
23. Until the LORD removed Israel out of his sight, as he had said by all his servants the prophets. So was Israel carried away out of their own land to Assyria unto this day.
24. And the king of Assyria brought men from Babylon, and from Cuthah, and from Ava, and from Hamath, and from Sepharvaim, and placed them in the cities of Samaria instead of the children of Israel: and they possessed Samaria, and dwelt in the cities thereof.
25. And so it was at the beginning of their dwelling there, that they feared not the LORD: therefore the LORD sent lions among them, which slew some of them.
26. Wherefore they spake to the king of Assyria, saying, The nations which thou hast removed, and placed in the cities of Samaria, know not the manner of the God of the land: therefore he hath sent lions among them, and, behold, they slay them, because they know not the manner of the God of the land.
27. Then the king of Assyria commanded, saying, Carry thither one of the priests whom ye brought from thence; and let them go and dwell there, and let him teach them the manner of the God of the land.
28. Then one of the priests whom they had carried away from Samaria came and dwelt in Bethel, and taught them how they should fear the LORD.
29. Howbeit every nation made gods of their own, and put them in the houses of the high places which the Samaritans had made, every nation in their cities wherein they dwelt.
30. And the men of Babylon made Succothbenoth, and the men of Cuth made Nergal, and the men of Hamath made Ashima,
31. And the Avites made Nibhaz and Tartak, and the Sepharvites burnt their children in fire to Adrammelech and Anammelech, the gods of Sepharvaim.
32. So they feared the LORD, and made unto themselves of the lowest of them priests of the high places, which sacrificed for them in the houses of the high places.
33. They feared the LORD, and served their own gods, after the manner of the nations whom they carried away from thence.
34. Unto this day they do after the former manners: they fear not the LORD, neither do they after their statutes, or after their ordinances, or after the law and commandment which the LORD commanded the children of Jacob, whom he named Israel;
35. With whom the LORD had made a covenant, and charged them, saying, Ye shall not fear other gods, nor bow yourselves to them, nor serve them, nor sacrifice to them:
36. But the LORD, who brought you up out of the land of Egypt with great power and a stretched out arm, him shall ye fear, and him shall ye worship, and to him shall ye do sacrifice.
37. And the statutes, and the ordinances, and the law, and the commandment, which he wrote for you, ye shall observe to do for evermore; and ye shall not fear other gods.
38. And the covenant that I have made with you ye shall not forget; neither shall ye fear other gods.
39. But the LORD your God ye shall fear; and he shall deliver you out of the hand of all your enemies.
40. Howbeit they did not hearken, but they did after their former manner.
41. So these nations feared the LORD, and served their graven images, both their children, and their children's children: as did their fathers, so do they unto this day.
1. Moreover the word of the LORD came unto me, saying,
2. Also, thou son of man, thus saith the Lord GOD unto the land of Israel; An end, the end is come upon the four corners of the land.
3. Now is the end come upon thee, and I will send mine anger upon thee, and will judge thee according to thy ways, and will recompense upon thee all thine abominations.
4. And mine eye shall not spare thee, neither will I have pity: but I will recompense thy ways upon thee, and thine abominations shall be in the midst of thee: and ye shall know that I am the LORD.
5. Thus saith the Lord GOD; An evil, an only evil, behold, is come.
6. An end is come, the end is come: it watcheth for thee; behold, it is come.
7. The morning is come unto thee, O thou that dwellest in the land: the time is come, the day of trouble is near, and not the sounding again of the mountains.
8. Now will I shortly pour out my fury upon thee, and accomplish mine anger upon thee: and I will judge thee according to thy ways, and will recompense thee for all thine abominations.
9. And mine eye shall not spare, neither will I have pity: I will recompense thee according to thy ways and thine abominations that are in the midst of thee; and ye shall know that I am the LORD that smiteth.
10. Behold the day, behold, it is come: the morning is gone forth; the rod hath blossomed, pride hath budded.
11. Violence is risen up into a rod of wickedness: none of them shall remain nor of their multitude, nor of any of theirs: neither shall there be wailing for them.
12. The time is come, the day draweth near: let not the buyer rejoice, nor the seller mourn: for wrath is upon all the multitude thereof.
13. For the seller shall not return to that which is sold, although they were yet alive: for the vision is touching the whole multitude thereof, which shall not return; neither shall any strengthen himself in the iniquity of his life.
14. They have blown the trumpet, even to make all ready; but none goeth to the battle: for my wrath is upon all the multitude thereof.
15. The sword is without, and the pestilence and the famine within: he that is in the field shall die with the sword; and he that is in the city, famine and pestilence shall devour him.
16. But they that escape of them shall escape, and shall be on the mountains like doves of the valleys, all of them mourning, every one for his iniquity.
17. All hands shall be feeble, and all knees shall be weak as water.
18. They shall also gird themselves with sackcloth, and horror shall cover them; and shame shall be upon all faces, and baldness upon all their heads.
19. They shall cast their silver in the streets, and their gold shall be removed: their silver and their gold shall not be able to deliver them in the day of the wrath of the LORD: they shall not satisfy their souls, neither fill their bowels: because it is the stumblingblock of their iniquity.
20. As for the beauty of his ornament, he set it in majesty: but they made the images of their abominations and of their detestable things therein: therefore have I set it far from them.
21. And I will give it into the hands of the strangers for a prey, and to the wicked of the earth for a spoil; and they shall pollute it.
22. My face will I turn also from them, and they shall pollute my secret place for the robbers shall enter into it, and defile it.
23. Make a chain: for the land is full of bloody crimes, and the city is full of violence.
24. Wherefore I will bring the worst of the heathen, and they shall possess their houses: I will also make the pomp of the strong to cease; and their holy places shall be defiled.
25. Destruction cometh; and they shall seek peace, and there shall be none.
26. Mischief shall come upon mischief, and rumour shall be upon rumour; then shall they seek a vision of the prophet; but the law shall perish from the priest, and counsel from the ancients.
27. The king shall mourn, and the prince shall be clothed with desolation, and the hands of the people of the land shall be troubled: I will do unto them after their way, and according to their deserts will I judge them; and they shall know that I am the LORD.
1. Now in the fifteenth year of the reign of Tiberius Caesar, Pontius Pilate being governor of Judaea, and Herod being tetrarch of Galilee, and his brother Philip tetrarch of Ituraea and of the region of Trachonitis, and Lysanias the tetrarch of Abilene,
2. Annas and Caiaphas being the high priests, the word of God came unto John the son of Zacharias in the wilderness.
3. And he came into all the country about Jordan, preaching the baptism of repentance for the remission of sins;
4. As it is written in the book of the words of Esaias the prophet, saying, The voice of one crying in the wilderness, Prepare ye the way of the Lord, make his paths straight.
5. Every valley shall be filled, and every mountain and hill shall be brought low; and the crooked shall be made straight, and the rough ways shall be made smooth;
6. And all flesh shall see the salvation of God.
7. Then said he to the multitude that came forth to be baptized of him, O generation of vipers, who hath warned you to flee from the wrath to come?
8. Bring forth therefore fruits worthy of repentance, and begin not to say within yourselves, We have Abraham to our father: for I say unto you, That God is able of these stones to raise up children unto Abraham.
9. And now also the axe is laid unto the root of the trees: every tree therefore which bringeth not forth good fruit is hewn down, and cast into the fire.
10. And the people asked him, saying, What shall we do then?
11. He answereth and saith unto them, He that hath two coats, let him impart to him that hath none; and he that hath meat, let him do likewise.
12. Then came also publicans to be baptized, and said unto him, Master, what shall we do?
13. And he said unto them, Exact no more than that which is appointed you.
14. And the soldiers likewise demanded of him, saying, And what shall we do? And he said unto them, Do violence to no man, neither accuse any falsely; and be content with your wages.
15. And as the people were in expectation, and all men mused in their hearts of John, whether he were the Christ, or not;
16. John answered, saying unto them all, I indeed baptize you with water; but one mightier than I cometh, the latchet of whose shoes I am not worthy to unloose: he shall baptize you with the Holy Ghost and with fire:
17. Whose fan is in his hand, and he will throughly purge his floor, and will gather the wheat into his garner; but the chaff he will burn with fire unquenchable.
18. And many other things in his exhortation preached he unto the people.
19. But Herod the tetrarch, being reproved by him for Herodias his brother Philip's wife, and for all the evils which Herod had done,
20. Added yet this above all, that he shut up John in prison.
21. Now when all the people were baptized, it came to pass, that Jesus also being baptized, and praying, the heaven was opened,
22. And the Holy Ghost descended in a bodily shape like a dove upon him, and a voice came from heaven, which said, Thou art my beloved Son; in thee I am well pleased.
23. And Jesus himself began to be about thirty years of age, being( as was supposed) the son of Joseph, which was the son of Heli,
24. Which was the son of Matthat, which was the son of Levi, which was the son of Melchi, which was the son of Janna, which was the son of Joseph,
25. Which was the son of Mattathias, which was the son of Amos, which was the son of Naum, which was the son of Esli, which was the son of Nagge,
26. Which was the son of Maath, which was the son of Mattathias, which was the son of Semei, which was the son of Joseph, which was the son of Juda,
27. Which was the son of Joanna, which was the son of Rhesa, which was the son of Zorobabel, which was the son of Salathiel, which was the son of Neri,
28. Which was the son of Melchi, which was the son of Addi, which was the son of Cosam, which was the son of Elmodam, which was the son of Er,
29. Which was the son of Jose, which was the son of Eliezer, which was the son of Jorim, which was the son of Matthat, which was the son of Levi,
30. Which was the son of Simeon, which was the son of Juda, which was the son of Joseph, which was the son of Jonan, which was the son of Eliakim,
31. Which was the son of Melea, which was the son of Menan, which was the son of Mattatha, which was the son of Nathan, which was the son of David,
32. Which was the son of Jesse, which was the son of Obed, which was the son of Booz, which was the son of Salmon, which was the son of Naasson,
33. Which was the son of Aminadab, which was the son of Aram, which was the son of Esrom, which was the son of Phares, which was the son of Juda,
34. Which was the son of Jacob, which was the son of Isaac, which was the son of Abraham, which was the son of Thara, which was the son of Nachor,
35. Which was the son of Saruch, which was the son of Ragau, which was the son of Phalec, which was the son of Heber, which was the son of Sala,
36. Which was the son of Cainan, which was the son of Arphaxad, which was the son of Sem, which was the son of Noe, which was the son of Lamech,
37. Which was the son of Mathusala, which was the son of Enoch, which was the son of Jared, which was the son of Maleleel, which was the son of Cainan,
38. Which was the son of Enos, which was the son of Seth, which was the son of Adam, which was the son of God.


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text:
Year : 2015 | Volume : 15 | Issue : 1 | Page : 2-7
SI Omoruyi1, AB Enogieru1, OI Momodu1, BA Ayinde2, BD Grillo1
1 Department of Anatomy, School of Basic Medical Sciences, University of Benin, Benin City, Edo State, Nigeria
2 Department of Pharmacognosy, Faculty of Pharmacy, University of Benin, Benin City, Edo State, Nigeria
S I Omoruyi
Department of Anatomy, School of Basic Medical Sciences, University of Benin, Benin City, Edo State
Keywords: Antioxidant, hepatotoxicity, Musanga cecropioides, paracetamol, serum enzymes
Omoruyi S I, Enogieru A B, Momodu O I, Ayinde B A, Grillo B D. Paracetamol-induced liver damage: Ameliorative effects of the crude aqueous extract of Musanga cecropioides. Niger J Health Sci 2015;15:2-7
Omoruyi S I, Enogieru A B, Momodu O I, Ayinde B A, Grillo B D. Paracetamol-induced liver damage: Ameliorative effects of the crude aqueous extract of Musanga cecropioides. Niger J Health Sci [serial online] 2015 [cited 2019 Jul 17];15:2-7. Available from: http://www.chs-journal.com/text.asp?2015/15/1/2/171381
Liver is the key organ regulating homeostasis in the body. It is involved with almost all the biochemical pathways related to growth, fight against disease, nutrient supply, energy provision, and reproduction.[1] More than 900 drugs have been implicated in causing liver injury [2] and it is the most common reason for a drug to be withdrawn from the market. Drug-induced liver injury is a potential complication of nearly every medication because the liver is central to the metabolic disposition of virtually all drugs and foreign substances.[2],[32]
Paracetamol which is safe for use at recommended doses (1000 mg per single dose and up to 3000 mg/day for adults, and up to 2000 mg/day if drinking alcohol). Moreover, it can as well cause potential fatal liver damage in cases of acute overdose and in rare individuals; a normal dose can do the same. The risk is heightened by alcohol consumption. An over dosage of paracetamol is known to be the cause of acute hepatic necrosis in both experimental animals [4],[32] and humans.[6],[32]
Paracetamol toxicity is caused by excessive use or overdose of the drug. It mainly causes liver injury. It is one of the most common causes of drug poisoning worldwide and the most common cause of acute liver failure in the United States and the United Kingdom.[8],[32]
Conventional synthetic drugs used in the treatment of liver diseases are sometimes inadequate and can have serious adverse effects. So there is a worldwide trend to go back to traditional medicinal plants.[10],[11],[12]Musanga cecropioides, R. Brown (Cecropiaceae), the African corkwood tree, also known as the Umbrellatree, is found mostly in the tropical forests of Africa stretching from Guinea to Congo. The plant is of high importance to local herbalist because of its diverse medicinal uses which include its use as oxytocic, contraceptive, antihypertensive, antidiabetic, analgesic, and diuretic.[13] Traditionally, the plant is used to induce labor.[14] In some parts of Edo and Delta states of Nigeria, the plant is used as antihelmintic and antidysenteric agent.[15] Among the Yoruba tribe of South-West, Nigeria, hot infusion of stem bark of the plant is also used for the treatment of fever, jaundice, acute gastric poisonings, and liver diseases.
In an earlier study, the mechanism of action involved in the hypotensive properties of the aqueous extract of the leaves of M. cecropioides was investigated.[16] Its antidiabetic and hypoglycemic effects have also been investigated.[17]
The aim of the present study was to examine the traditional assumption of the hepatoprotective efficacy of M. cecropioides in the treatment of liver diseases resulting from poisonings and to explicate its possible mechanism of action using paracetamol-induced liver damage in experimental rat models.
The School of Basic Medical Sciences, University of Benin, granted ethical approval for the study.
Plant material
Fresh bark of stem of the M. cecropioides was collected from a deciduous forest around Oluku area within Benin city during the month of September 2011. The plant was identified by Mr. Sunny Nweke of the Department of Pharmacognosy, Faculty of Pharmacy, University of Benin and authenticated at the Forest Research Institute of Nigeria, Ibadan, Nigeria where a herbarium specimen number FHT106428 had been deposited initially.
The sheaths were washed with normal saline, sorted, air-dried at room temperature and protected from direct sunlight and heat for 2 weeks until completely air-dried. They were then pulverized using the laboratory hammer-mill and the powdered samples were stored in air and water-proof containers until required for extraction.
Preparation of aqueous extract
Approximately, 2.0 kg of the powder of bark of stem of M. cecropioides was extracted over 24 h using 2 L of distilled water. The mixture was filtered using Whatman filtered paper, and the filtrate evaporated at 60°C using a vacuum rotary evaporator (Buchi, Switzerland). The moist residue was freeze-dried using a vacuum freeze-drier and stored in a desicator. It was preserved in a refrigerator at 4°C until needed. The crude extract was dissolved in double distilled water to make a concentration of 100 mg/ml from which different doses of 250 and 500 mg/kg body weight by oral route were reconstituted.
Preliminary phytochemical screening
Phytochemical screenings were performed using standard procedures by Odebiyi and Sofowora [18] and Trease and Evans.[19] The phytochemicals were screened for anthraquinones, cardiac glycosides, saponins, flavonoids, tannins, alkaloids, phlobotannins, and terpenoids.
Experimental animals
A total of 30 adult male Wistar rats of average weight 250 g were used for this study. The animals were inbred rats obtained from the rat Colony of the Animal House, Department of Anatomy, University of Benin, Benin city. The animals were maintained on grower's marsh manufactured by Bendel Feeds and Flour Mills Limited, Ewu, Edo state, Nigeria and potable water which were made available adlibitum. The rats were maintained at an ambient temperature between 28°C and 30°C, humidity of 55% ± 5%, and standard natural photo period of approximately 12 h of light (06:30 h–18:30 h) alternating with approximately 12 h of darkness (18:30 h–06:30 h).
Chemicals and reagents
Normal saline was manufactured by Unique Pharmaceuticals, Sango-Otta, Nigeria and Paracetamol tablets by Emzor Pharmaceuticals Industries Ltd., Isolo, Lagos, Nigeria. Other reagents were all of analytical grade.
Induction of paracetamol hepatotoxicity
The animals were divided into five groups of A, B, C, D, and E. Group A animals served as the controls and were given 10 ml/kg of normal saline. Animals in groups B, C, D, and E were given paracetamol at 500 mg/kg of body weight through orogastric route using a metal cannula. The animals in group C were pretreated with 25 mg/kg of body weight of silymarin before the administration of paracetamol during the period of the experiment. Similarly, animals in groups D and E were pretreated with 250 and 500 mg/kg of body weight of the aqueous crude stem bark extract of M. cecropioides via oral route 1 h before the administration of paracetamol. The chosen dose for paracetamol was based on previous research by Gupta et al.[20] All treatments were given daily for 14 days and animals were sacrificed on day 15 by cervical dislocation after anesthesia.
Assay for hepatic marker enzymes
The blood samples were collected via cardiac puncture and stored in plain bottles. The blood samples were centrifuged at 3000 revolutions/min using a table-top centrifuge (Shanghai Surgical Instrument Factory, Shanghai, China) at 37°C for 15 min to separate the sera. Serum alanine (ALT), aspartate (AST) amino-transferases, alkaline phosphatase (ALP) as well as total protein (TP) were assayed spectrophotometrically, using Randox colorimetric assay diagnostic kits (Randox, Northern Ireland).
Assay for antioxidant enzymes
After sacrifice, the liver tissues were excised and a part chopped off to be homogenized in a mortar and pestle with a pinch of acid washed sand and a total of 5 ml of normal saline (0.9% saline) added sequentially during the homogenization process. The homogenates were centrifuged at 3500 rpm for 5 min with the aid of a centrifuge. The clear supernatants were collected using a micropipette and transferred into an empty specimen container and refrigerated until needed for the assays. Assay for superoxide dismutase (SOD) was done using the method of Misra and Fridovich [21] while the method of Cohen et al.[22] was used for catalase (CAT) activity. Finally, assay for lipid peroxidation and malondialdehyde (MDA) was done using the method of Varshney and Kale.[23]
Histopathological studies
The liver tissues of the rats were carefully dissected out and freed from the supporting adipose tissue and ligaments. After rinsing the liver in normal saline, different sections were taken from each lobe and the tissues were processed for routine hematoxylin and eosin (H and E) staining using the method of Drury et al.[24] Briefly, the excised tissues were fixed in 10% formal saline for 24 h, processed by paraffin embedding method and sections of 5 µ thickness were cut. The sections were for H and E demonstration of liver histoarchitecture under a light microscope. Photomicrographs of the desired area of liver sections were captured using the research microscope domiciled in the Department of Anatomy, School of Basic Medical Sciences, University of Benin, Benin city.
Weights and biochemical assay values were presented as mean (standard error of means). Data analysis was carried out using Statistical Package for Social Sciences, version 17, Manufactured by International Business Machine Corporation. The significance of difference in the means of all parameters was determined using one-way analysis of variance with 95% confidence interval. Least square difference and posthoc test was carried out for all groups in comparison with the control group. Statistical significance was set at P < 0.05.
Phytochemical screening
Results of the phytochemical screening are shown in [Table I]. The bark of stem of M. cecropioides was fond to contain cardiac glycosides, saponins, flavonoids, tannins, plobatanins, and terpenoids (+). Alkaloids and anthraquinones were not observed to be absent (−).
Table I: Results of phytochemical screening are shown
The results of AST, ALT, and ALP in control rats are presented in [Table II]. The means of levels of AST, ALT, and ALP in control rats were 34.33 (1.45), 25 (1.53), and 70.00 (1.88) IU/L, respectively, whereas in paracetamol treated rats, these levels were elevated to 83.50 (1.50), 87.50 (1.50), and 151.67 (2.33) IU/L, respectively. M. cecropioides pretreatment at the dose 250 mg/kg significantly reduced the paracetamol-induced rise in the AST, ALT, and ALP (P < 0.05). The mean values in the treated were minimized to 53.33 (2.56), 63.00 (2.21), and 93.50 (2.06) IU/L, respectively, when compared with paracetamol treated group. With a higher dose of 500 mg/kg M. cecropioides further reduction mean values of AST, ALT, and ALP to 42.83 (1.80), 47.47 (2.12), and 88.17 (2.68) IU/L, were recorded, respectively. Pretreatment with Silymarin at 25 mg/kg also prevented the paracetamol-induced rise in the means of AST, ALT, and ALP with mean values of 38.67 (1.28), 63.00 (2.21), and 83.83 (2.259) IU/L recorded, respectively. The same trend was observed in TP values [Table II].
Table II: Effect of Musanga cecropioides aqueous extract of bark of stem on biochemical parameters in paracetamol--induced hepatotoxicity in rats
The liver SOD and CAT observed in control rats were 30.17 (1.51) and 29.00 (1.34) IU/L, respectively, whereas MDA was 14.17 (1.96) IU/L. However, significant changes were noted in paracetamol treated groups, as SOD and CAT were reduced to 18.83 (2.99) and 17.33 (1.80) IU/L, respectively, whereas MDA was increased to 25.33 (2.17) IU/L. M. cecropioides pretreatment (250 mg/kg and 500 mg/kg) also significantly reversed paracetamol-induced changes in SOD (21.67 [1.26] and 25.33 [1.17] IU/L), CAT (19.33 [1.45] and 23.67 [1.78] IU/L); and MDA (22.40 [1.60]; 19.97 [1.74] IU/L, respectively. Similar findings were observed with silymarin [Table II].
Histopathological findings are shown in [Figure 1] for controls and exposed rats. Histopathological findings revealed that the administration of paracetamol resulted in necrosis of hepatocytes as well as deposition of fats in the tissues [Figure 1], plate 2] when compared with controls [Figure 1], plate 1], but the severity was reduced in those groups of animals pretreated with 25 mg/kg of silymarin, 500 mg/kg and 250 mg/kg of the crude aqueous extract of bark of stem of M. cecropioides [Figure 1], plates 3-5]. The fatty deposition appeared as empty spaces or vacuoles as fat deposits were not stained for during routine H and E staining.
Figure 1: The histopathological findings in the controls and the exposed rats.
This study evaluated the potential hepatoprotective role of M. cecropioides in paracetamol-induced liver damage in rats. Damage to the liver or hepatotoxicity did not result from paracetamol itself, but from one of its metabolites, N-acetyl-p-benzoquinone imine (NAPQI). NAPQI is known to deplete the liver's natural antioxidant glutathione and directly damage cells in the liver, leading to liver failure.[25] Many hepatoxins could induce liver injury through oxidative stress, inflammation, fibrogenesis and liver necrosis.[26] Acute injury to hepatocytes alters their transport function and membrane permeability, leading to leakage of marker enzymes from the cells.[27]
In the assessment of liver damage caused by paracetamol, the determination of enzyme levels such as AST, ALT in the serum is largely used. Necrosis or membrane damage releases the enzyme into circulation and, hence, it can be measured in the serum. A high level of AST is a marker of liver damage as AST catalyses, the conversion of alanine to pyruvate and glutamate and is released in a similar manner. Therefore, ALT is more specific for the liver, and is thus a better parameter for detecting liver injury. Elevated levels of serum enzymes are indicative of cellular leakage and loss of functional integrity of cell membrane in the liver.[28] Serum ALP and TP levels on other hand are related to the function of hepatic cells. Increase in serum level of ALP is due to increased synthesis, in the presence of increasing biliary pressure.[29] Thus, an effective control of ALP activity is necessary and this points toward an early improvement in the secretory mechanism of the hepatic cell.
Results from the present study showed a significant elevation of ALP, AST, and ALT levels in paracetamol treated rats when compared to controls, but on pretreatment with graded doses of M. cecropioides, induced rises in ALP, AST, and ALT from paracetamol treatment was much reduced and this was statistically significant (P < 0.05) when compared with paracetamol treated group pretreatment with graded doses of M. cecropioides. TP levels of paracetamol treated animals dropped significantly, but there was a significant increase in animals on pretreatment with graded doses of M. cecropioides (P < 0.05) as TP levels were found to be approaching the normal value. Silymarin at 25 mg/kg of body weight also prevented the induced rises of ALP, AST, and ALT levels as a result of paracetamol treatment and also resulted in a significant increase in TP levels when compared with animals treated with only paracetamol.
Biological systems protect themselves against the damaging effects of activated species by several means. These include free radical scavengers and chain reaction terminators; enzymes such as SOD, CAT, and glutathione peroxidase (GPx) system.[30] It is known that SOD removes superoxide by converting it to H2O2, which can be rapidly converted to water by CAT and GPx.[31] However, oxidative stress results in toxicity when the rate at which the reactive oxygen species are generated exceeds the cell capacity for their removal and this leads to lipid peroxidation which is an autocatalytic process, and a common consequence of cell death. One of the end products in the lipid peroxidation process is MDA.[32] Decrease in enzyme activity of SOD is a sensitive index in hepatocellular damage and is the most sensitive enzymatic index in live injury.[33] Liver is a major site with its highest activity of CAT, an enzymatic antioxidant which is also widely distributed in all animal tissues. A function of CAT is to decompose hydrogen peroxide and protect the tissues from highly reactive hydroxyl radicals.[34] It is, therefore, worthy of note that a reduction in the activity of CAT may result in a number of harmful effects due to the assimilation of superoxide radical and hydrogen peroxide. Result from the present study showed that administration of a higher dose of M. cecropioides (500 mg/kg) increased the level of CAT activity to almost that produced by silymarin, the standard hepatoprotective drug. This prevented the accumulation of excessive free radicals and protected the liver from toxicity initiated by paracetamol intoxication.
The increase in MDA levels in liver suggests enhanced lipid peroxidation leading to tissue damage and failure of antioxidant defense mechanisms to prevent the formation of excessive free radicals. Lipid peroxidation has been postulated to be the basis of destructive process of liver injury due to paracetamol intoxication. In the present study, the elevations in the levels of end products of lipid peroxidation in the liver of rat treated with paracetamol were observed to be high but pretreatment with M. cecropioides significantly reversed these changes. Hence, it is possible that the mechanism of hepatic protection by M. cecropioides is due to its antioxidant effect.
Results of histopathological studies support the results of biochemical parameters analyzed in the present study as the control group of animals showed normal architecture of the liver and integrity of the hepatocytes. However, histological analyses of livers of rats treated with paracetamol showed significant hepatotoxicity, characterized by necrosis, vacuolization of hepatocytes, inflammatory hepatic tissues, including the presence of moderate infiltration of inflammatory cells. Furthermore, pretreatment with Silymarin and M. cecropioides, reduced the severity of these damages. The empty spaces or vacuoles in the paracetamol treated groups were as a result of fat deposition in the liver parenchyma and this indicated early stage of fatty liver.
From preliminary phytochemical studies, it was shown that M. cecropioides contains flavonoids, triterpenoids, and steroids and these were in consonance with the results of the work reported by Kadiri and Ajayi.[35] A number of scientific reports indicated certain flavonoids, triterpenoids, and steroids have protective effect on liver cells due to its antioxidant properties.[36],[37],[38] The presence of these compounds in the extract may be responsible for its protective role in paracetamol-induced liver damage in rats. Hence, the results from the present study support the use of M. cecropioides in folklore practice in the treatment of liver infection and other liver diseases as it exerts significant hepatic protection against paracetamol-induced liver toxicity.
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[Figure 1]
[Table I], [Table II]
Omoruyi S I
Enogieru A B
Momodu O I
Ayinde B A
Grillo B D
hepatotoxicity
Musanga cecropioides
serum enzymes

redpajama_set_name: RedPajamaCommonCrawl