Hepatoprotective Effect Of Prazosin Is Comparable To N-Acetylcysteine In Acetaminophen Induced Hepatotoxicity In Mice.

BACKGROUND: Autonomic nervous system modulates acetaminophen induced hepatotoxicity. The purpose of the study was to determine the hepatoprotective effect of α1 antagonist (prazosin) and ß2 agonist (salbutamol) on acetaminophen induced hepatotoxicity in mice. METHODS: This experimental study was conducted at Post Graduate Medical Institute, Lahore in which 50 adult mice were divided in to five groups. With the exception of normal control, hepatotoxicity was induced in all other study groups by giving single intraperitoneal injection of acetaminophen 300 mg/ kg. First and second groups served as normal and toxic control were given distilled water 6 ml/ kg while third, fourth and fifth experimental groups were given N-acetylcysteine (300 mg/ kg), prazosin (0.18 mg/ kg) and salbutamol (0.35 mg/kg) intraperitoneally at 2,4 and 8 hours after acetaminophen injection. Serum liver enzymes were analysed at 0 and 72 hours while histopathological finding were assessed at the end of study by using SPSS-20. RESULTS: All the groups treated with toxic dose of acetaminophen showed significant increase in serum ALT, i.e., B (Toxic control 3372%), C (NAC treated 282%), D (Prazosin treated 582%), E(Salbutamol treated 3297%) and AST levels, i.e., B (Toxic control 2750% ), C (NAC treated 230% ), D (Prazosin treated 280%), E (Salbutamol treated 828%) with p-value ˂0.001. When this increase was compared between groups, the lowest increase in serum ALT and AST levels was observed in Nacetylcysteine and prazosin group with no significant difference. Similarly, experimental animals receiving prazosin and N-acetylcysteine had the lowest inflammation, degeneration and necrosis scores than the toxic control group in histopathological analysis of the liver with p-value <0.001. CONCLUSIONS: The hepatoprotective effect of prazosin is comparable to N- acetylcysteine against acetaminophen induced hepatotoxicity in mice.

Pioglitazone attenuates cardiometabolic risk factors in non-diabetic patients with dyslipidemia.

OBJECTIVE: To determine the effect of pioglitazone on cardiometabolic risk factors in non-diabetic patients with dyslipidaemia. METHODS: This prospective, randomised clinical trial was conducted at Sheikh Zayed Medical College and Hospital, Rahim Yar Khan, Pakistan, from August to October 2016, and comprised non-diabetic patients with dyslipidaemia. They were randomly divided into three groups. First and second groups were given a daily dose of tab pioglitazone 30mg and gemfibrozil 600mg, respectively, while the third group served as the healthy control. Body weight, body mass index and serum lipid profile were analysed pre- and post-treatment. SPSS 16 was used for data analysis. RESULTS: Of the 135 participants, there were 45(33.3%) in each group. After 12 weeks' treatment, the pioglitazone group showed a highly significant reduction in body weight (83±10.5 to 76±13.5kg) and body mass index (27.7±4.4 to 25.5±6.4kg/m2) (p<0.01) compared to the gemfibrozil group. The pioglitazone group showed a significant improvement in serum lipid profile after 12 weeks (p<0.05) while the gemfibrozil group showed a highly significant improvement in serum lipid profile (p<0.01). CONCLUSIONS: Pioglitazone independently improved cardiometabolic risk factors, even in non-diabetics.