Protective Effects of Omega-3 Fatty Acids Against Cisplatin Induced Hepatocellular Damage and Oxidative Stress in Rats

Abstract

Cisplatin has a high rate of effectiveness in treating cancer, its use is restricted due to the severe adverse consequences it produces. Nephrotoxicity, neurotoxicity, and ototoxicity are only a few of the unwanted side effects. In the case of cisplatin, hepatotoxicity is thought to be caused by oxidative stress brought on by an increase in reactive oxygen species (ROS). Omega-3 is an antioxidant that reduces the production of reactive oxygen species by inhibiting the enzyme nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. This study aimed to compare the beneficial effects of omega-3 therapy against the harmful effects of cisplatin-induced hepatotoxicity and to determine the effect of cisplatin on hepatic pro-oxidant or antioxidant systems. The rats were divided into four groups (n = 6 per group) and treated with single dosages of cisplatin (5 milligrams per kilogram) and omega-3 (20 milligrams per kilogram over fourteen days by intraperitoneal administration), or cisplatin combined with omega-3. In addition, the rat’s blood was tested for alkaline phosphatase, aspartate transaminase, and alanine transaminase levels. We observed higher levels of lipid peroxidation products, total oxidant status, and ALT in the cisplatin group compared to the control group. Conversely, it was revealed that glutathione peroxidase and superoxide dismutase levels were considerably lower in the cisplatin group compared to the control group. Omega-3 has significantly reduced the toxicity of cisplatin in the liver. Our biochemical results confirmed our histological observations of central venous dilations, pericenter and periportal sinusoidal dilations, parenchymal inflammation, vacuolar abnormalities in hepatocytes, biliary duct proliferation, and caspase-3 positive hepatocytes. In conclusion, Omega-3 can provide biochemical and histological protection against cisplatin-induced hepatotoxicity.