Limits...
Effect of subclinical, clinical and supraclinical doses of calcium channel blockers on models of drug-induced hepatotoxicity in rats.

Okwa IB, Akindele AJ, Agbaje EO, Oshinuga OT, Anunobi CC, Adeyemi OO - EXCLI J (2013)

Bottom Line: The hepatotoxicants significantly increased serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP), as well as duration of sleep in the hypnosis test.These drugs significantly reduced the hepatic levels of reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and increased the level of malondialdehyde (MDA).The CCBs at the various doses significantly reversed the effects of isoniazid-rifampicin, zidovudine and erythromycin.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology, Faculty of Basic Medical Sciences, College of Medicine, University of Lagos, P.M.B. 12003, Lagos, Nigeria.

ABSTRACT
Drug-related hepatotoxicity is the leading cause of acute liver failure, and hepatic problems are responsible for a significant number of liver transplantations and deaths worldwide. Calcium has been associated with various metabolic processes that lead to cell death and apoptosis, and increased cytosolic Ca(2+) has been implicated in hepatotoxicity. This study was designed to investigate the effects of calcium channel blockers (CCBs) on isoniazid-rifampicin, zidovudine and erythromycin-induced hepatotoxicity in rats. Treatment groups comprised control, hepatotoxicant, hepatotoxicant along with each of silymarin, nifedipine, verapamil and diltiazem at subclinical, clinical and supraclinical doses. A day to the end of treatment for each model, rats were subjected to the hexobarbitone-induced hypnosis test. On the last days of treatment, blood samples were collected and serum was analyzed for relevant biochemical parameters. Animals were sacrificed after blood collection and livers were harvested, and samples obtained for in vivo antioxidant indices assay and histopathology. The hepatotoxicants significantly increased serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP), as well as duration of sleep in the hypnosis test. These drugs significantly reduced the hepatic levels of reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and increased the level of malondialdehyde (MDA). The CCBs at the various doses significantly reversed the effects of isoniazid-rifampicin, zidovudine and erythromycin. The results obtained in this study suggest that the CCBs possess hepatoprotective activity in drug-induced hepatotoxicity and may be beneficial at the subclinical and clinical doses.

No MeSH data available.


Related in: MedlinePlus

Effect of nifedipine, verapamil and diltiazem on duration of sleep in hexobarbitone-induced hypnosis test in erythromycin-induced hepatotoxicity in rats
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4552102&req=5

T10: Effect of nifedipine, verapamil and diltiazem on duration of sleep in hexobarbitone-induced hypnosis test in erythromycin-induced hepatotoxicity in rats

Mentions: In relation to control, erythromycin significantly (P < 0.001) increased the duration of sleep. Silymarin and the CCBs at all doses used significantly (P < 0.001) reduced the duration of sleep compared to erythromycin. The effect of the CCBs in preserving the metabolizing effect of cytochrome P450 enzymes on hexobarbitone was most pronounced for nifedipine at the subclinical dose of 0.17 mg/kg, for verapamil at the clinical dose of 4.30 mg/kg, and for diltiazem at the subclinical dose of 0.68 mg/kg (Table 10(Tab. 10)).


Effect of subclinical, clinical and supraclinical doses of calcium channel blockers on models of drug-induced hepatotoxicity in rats.

Okwa IB, Akindele AJ, Agbaje EO, Oshinuga OT, Anunobi CC, Adeyemi OO - EXCLI J (2013)

Effect of nifedipine, verapamil and diltiazem on duration of sleep in hexobarbitone-induced hypnosis test in erythromycin-induced hepatotoxicity in rats
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4552102&req=5

T10: Effect of nifedipine, verapamil and diltiazem on duration of sleep in hexobarbitone-induced hypnosis test in erythromycin-induced hepatotoxicity in rats
Mentions: In relation to control, erythromycin significantly (P < 0.001) increased the duration of sleep. Silymarin and the CCBs at all doses used significantly (P < 0.001) reduced the duration of sleep compared to erythromycin. The effect of the CCBs in preserving the metabolizing effect of cytochrome P450 enzymes on hexobarbitone was most pronounced for nifedipine at the subclinical dose of 0.17 mg/kg, for verapamil at the clinical dose of 4.30 mg/kg, and for diltiazem at the subclinical dose of 0.68 mg/kg (Table 10(Tab. 10)).

Bottom Line: The hepatotoxicants significantly increased serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP), as well as duration of sleep in the hypnosis test.These drugs significantly reduced the hepatic levels of reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and increased the level of malondialdehyde (MDA).The CCBs at the various doses significantly reversed the effects of isoniazid-rifampicin, zidovudine and erythromycin.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology, Faculty of Basic Medical Sciences, College of Medicine, University of Lagos, P.M.B. 12003, Lagos, Nigeria.

ABSTRACT
Drug-related hepatotoxicity is the leading cause of acute liver failure, and hepatic problems are responsible for a significant number of liver transplantations and deaths worldwide. Calcium has been associated with various metabolic processes that lead to cell death and apoptosis, and increased cytosolic Ca(2+) has been implicated in hepatotoxicity. This study was designed to investigate the effects of calcium channel blockers (CCBs) on isoniazid-rifampicin, zidovudine and erythromycin-induced hepatotoxicity in rats. Treatment groups comprised control, hepatotoxicant, hepatotoxicant along with each of silymarin, nifedipine, verapamil and diltiazem at subclinical, clinical and supraclinical doses. A day to the end of treatment for each model, rats were subjected to the hexobarbitone-induced hypnosis test. On the last days of treatment, blood samples were collected and serum was analyzed for relevant biochemical parameters. Animals were sacrificed after blood collection and livers were harvested, and samples obtained for in vivo antioxidant indices assay and histopathology. The hepatotoxicants significantly increased serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP), as well as duration of sleep in the hypnosis test. These drugs significantly reduced the hepatic levels of reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and increased the level of malondialdehyde (MDA). The CCBs at the various doses significantly reversed the effects of isoniazid-rifampicin, zidovudine and erythromycin. The results obtained in this study suggest that the CCBs possess hepatoprotective activity in drug-induced hepatotoxicity and may be beneficial at the subclinical and clinical doses.

No MeSH data available.


Related in: MedlinePlus