Melatonin inhibira lipidnu peroksidaciju u jetri štakora uzrokovanu benzenom

We studied the antioxidative role of melatonin against benzene toxicity in rat liver. The inhibition of mitochondrial and microsomal lipid peroxidation differed between 24-hour (single-dose), 15-day, and 30-day treatments. Inhibition of mitochondrial lipid peroxidation was the highest after the single dose of melatonin, whereas highest microsomal inhibition was recorded after 30 days of melatonin treatment. No signifi cant difference was recorded between 15-day and 30-day treatments. Cytochrome P4502E1 (CYP4502E1) activity declined after the single-dose and 15-day melatonin treatment in the benzenetreated group, but it rose again, though not signifi cantly after 30 days of treatment. Liver histopathology generally supported these fi ndings. Phenol concentration in the urine samples declined in melatonin and benzene-treated rats. Our results show that melatonin affects CYP4502E1, which is responsible for benzene metabolism. Inhibition of its metabolism correlated with lower lipid peroxidation. In conclusion, melatonin was found to be protective against lipid peroxidation induced by benzene.Istražena je antioksidacijska uloga melatonina u zaštiti protiv toksičnoga djelovanja benzena u jetri štakora. Utvrđeno je da kratkoročno odnosno dugoročnije liječenje štakora melatoninom u različitoj mjeri štiti štakore istodobno izložene benzenu. Inhibicija lipidne peroksidacije mitohondrija i mikrosoma bila je različita nakon 24 h, 15 dana, odnosno 30 dana liječenja melatoninom. Najveća inhibicija lipidne peroksidacije mitohondrija zamijećena je nakon primjene jednokratne doze melatonina, dok je najizraženija inhibicija u mikrosomima zamijećena nakon 30 dana liječenja melatoninom. Slična istraživanja pokazuju da razina glutationa (GSH) najviše raste nakon 24 h liječenja melatoninom. Nije zamijećena razlika između liječenja u trajanju od 15 odnosno 30 dana. U štakora koji su uz benzen istodobno primali i melatonin razine citokroma P4502E1 pale su nakon 24 h odnosno 15 dana izloženosti. U štakora koji su primali samo melatonin te su razine nakon 30 dana statistički neznačajno porasle u odnosu na skupinu izloženu samo benzenu. Histopatološka analiza jetre načelno je potvrdila ove nalaze. Koncentracije fenola u mokraći bile su niže u štakora koji su istodobno primali melatonin i benzen. Ovi rezultati pokazuju da melatonin utječe na citokrom P4502E1, koji je odgovoran za metabolizam benzena. Inhibira li se njegov metabolizam, smanjuje se lipidna peroksidacija. Zaključak je da melatonin štiti od lipidne peroksidacije uzrokovane benzenom

Protective effects of caffeic acid phenethyl ester and thymoquinone on toluene induced liver toxicity.

Toluene is an organic solvent that is toxic to humans. Caffeic acid phenethyl ester (CAPE) and thymoquinone (TQ) exhibit antioxidant and antitoxic effects. We investigated the protective effects of CAPE and TQ on toluene induced hepatotoxicity. Wistar albino rats were divided into seven groups of eight. The animals were injected intraperitoneally (i.p.) with 0.1 ml/10 g/day corn oil (control I), 0.1 ml/10 g/day corn oil + 2 ml/kg/day 10% ethanol (control II), 20 mg/kg/day TQ dissolved in 0.1 ml/10 g corn oil (TQ), 10 µmol/kg/day CAPE dissolved in 10% ethanol (CAPE), 500 mg/kg/day toluene (T), toluene and TQ together (T + TQ), or toluene and CAPE together (T + CAPE). All rats were sacrificed on day 15. Liver samples were obtained for histological analysis. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were measured to evaluate liver function. Liver sections from the control I and TQ groups exhibited normal histology. Sections from the T group exhibited sinusoid dilation, hemorrhage, vacuolization and necrosis. TQ and CAPE protected against toluene induced histopathological changes. AST and ALT levels were increased significantly in T group compared to both control groups. CAPE decreased significantly the toluene induced increase in AST and ALT levels, while TQ did not. CAPE and TQ exhibited some antitoxic and hepato-protective effects on toluene induced liver damage