Acute inflammation can activate macrophages or monocytes and subsequently release several inflammatory cytokines and reactive oxygen species (ROS). Oxidative stress triggered by the production of ROS plays deleterious role leading to multiple organ failure. This study was designed to investigate the prophylactic effect of alpha-crystallin, a major chaperone lens protein comprising of alpha-A and alpha-B subunits in inflammation-induced mice. Mice were divided into three groups (n=6 in each): control, inflammation and alpha-crystallin-treated. Results show that ROS was significantly higher in the lymphocytes, hepatocytes and astrocytes (P<0.05) of inflammation-induced mice when compared to control, but no significant changes were observed in the alpha-crystallin-treated group. Increased level of lipid peroxidation (LPO) and decreased activities of antioxidant such as superoxide dismutase (SOD), catalase, glutathione peroxidase and glutathione were observed in the inflammation-induced mice when compared to control, whereas the activities of these were found to be normal followed by alpha-crystallin treatment. We also observed a reduction in reduced glutathione levels in hepatocytes of inflammation-induced mice, which were normalized on alpha-crystallin treatment. The in vitro study has shown that alpha-crystallin treatment not only suppresses the increase in LPO levels but also inhibits the lipid breakdown resulting from autooxidation in mouse cerebral cortex homogenate, and strongly suggests that alpha-crystallin therapy may serve as a potent pharmacological agent in systemic inflammation.

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.