Therefore, inhibiting BSEP should cause cytotoxic bile salts to accumulate in hepatocytes, leading to liver injury and impaired bile flow. Indeed, there is a strong association between BSEP inhibition and cholestasis in humans, and BSEP inhibitors are shown to induce cholestasis in vitro. However, hepatocytes have safety mechanisms that can compensate for impaired canalicular bile efflux. In response to cholestasis, MRP3 and MRP4 on the basolateral membrane are upregulated to allow efflux of accumulated bile salts into portal blood. Similarly, MRP2 can accommodate additional bile flow across the apical membrane in cholestatic conditions. These compensatory mechanisms explain why some BSEP inhibitors do not cause cholestasis. On the contrary, contrast, drugs that inhibit both MRP3/4 and BSEP (e.g., rifampicin, troglitazone, bosentan) pose greater risk for cholestasisMDR3 is another key canalicular efflux transporter that is the target of inhibition by certain drugs. MDR3 secretes phosphatidylcholine into bile canaliculi, where it form micelles with bile salts to dissolve cholesterol as well as protect hepatocyte and cholangiocytes from damage by bile salts. MDR3 inhibition leads to low phospholipid concentrations in bile that damages cholangiocytes and leads to cholestasis. Antifungal azoles such itraconazole have been shown to inhibit both MDR3 and BSEP,  thus giving them higher cholestatic potential. Other MDR3-inhibiting drugs are chlorpromazine, imipramine, haloperidol, ketoconazole, saquinavir, clotrimazole, ritonavir, and troglitazone.Another target for inhibition, MRP2 is an apical efflux transporter that mainly exports bilirubin glucuronide and glutathione into bile.
Patients with Dhat condition most normally ascribe their semen misfortune (secretion of semen in urine) to reasons like inordinate masturbation, sensual dreams, and unreasonable sexual longing. Nocturnal emission and secretion of semen in urine are considered to be the most widely recognized symptoms of semen misfortune. Patients with Dhat condition frequently dread the result of semen misfortune and regularly have the conviction that it will lead to decrease in sexual performance. The most widely recognized side effects in patients with Dhat condition are shortcoming of the body, sluggishness, low energy, and low temperament. Premature ejaculation and impotence are commonly seen. Other somatic symptoms like weakness, easy fatiguability, palpitations, insomnia, low mood, guilt and anxiety are often present. Males sometimes report a subjective feeling that their penises have shortened. These symptoms are usually associated with an anxious and dysphoric mood state. Another sign of this syndrome is white discharge. According to Ayurvedic, an Indian medical system, men who have experienced this have shown signs of anxiety issues. This disease is a culture bound syndrome. Semen loss is generally viewed as taboo and harmful. It is also associated with a lower socioeconomic class. Being able to produce semen is viewed as longevity of ones health and certain powers. In Indian culture, it is important for a man to produce semen. Treatment
Cognitive behavioral therapy is the mainstay of treatment. At other times counseling, anti-anxiety and antidepressant medications have been shown to be of use.