Antioxidants are substances that may protect cells from the damage caused by unstable molecules such as free radicals. Flavonoids are phenolic substances widely found in fruits and vegetables. The previous studies showed that the ingestion of flavonoids reduces the risk of cardiovascular diseases, metabolic disorders, and certain types of cancer. These effects are due to the physiological activity of flavonoids in the reduction of oxidative stress, inhibiting low-density lipoproteins oxidation and platelet aggregation, and acting as vasodilators in blood vessels. Free radicals are constantly generated resulting in extensive damage to tissues leading to various disease conditions such as cancer, Alzheimer's, renal diseases, cardiac abnormalities, etc., Medicinal plants with antioxidant properties play a vital functions in exhibiting beneficial effects and employed as an alternative source of medicine to mitigate the disease associated with oxidative stress. Flavonoids have existed over one billion years and possess wide spectrum of biological activities that might be able to influence processes which are dysregulated in a disease. Quercetin, a plant pigment is a potent antioxidant flavonoid and more specifically a flavonol, found mostly in onions, grapes, berries, cherries, broccoli, and citrus fruits. It is a versatile antioxidant known to possess protective abilities against tissue injury induced by various drug toxicities.

Objective: To study the effect of quercetin on methotrexate induced toxicity and to observe the histopathological changes. Materials and Methods: Thirty male rats were divided into 5 different groups with each group consisting of six rats. The Group I was a control and they were treated with 10 ml/kg of carboxymethyl cellulose. The Group II, III, IV and V animals were treated with methotrexate 0.125 mg/kg; methotrexate 0.25 mg/kg; methotrexate (0.125 mg/kg) + quercetin (500 mg/kg); and methotrexate (0.25 mg/kg) + quercetin (500 mg/kg), respectively. All drugs were administered orally through oral gavage once daily for 14 days. At the end of the study, blood samples were collected from all the animals in each group. The animals were then sacrificed and organs were collected for histopathological analysis. Results: Methotrexate 0.125 and 0.25 mg/kg significantly increased the levels of liver enzymes such as AST, ALT, ALP and total protein and renal markers such as urea and creatinine. The animals treated with quercetin along with methotrexate showed significant improvement on methotrexate induced liver and renal toxicities. Methotrexate significantly reduced the levels of haemoglobin and blood sugar and which was partially reversed by quercetin. The notable histopathological changes in lungs, liver and kidneys were observed with methotrexate treated animals and this was protected by quercetin. Conclusion: Methotrexate produced significant pathological changes at 0.250 mg/kg and possible ameliorative effect of quercetin observed in lung, liver and kidney. Quercetin 500 mg/kg significantly inhibited the methotrexate induced toxicity in liver and kidneys.