Hepato-renal Protective Effect of Glutamine in Oxidative Stress Rat Model by Elevating the Glutamine-Glutathione Axis

Toxic compounds such as carbon tetra chloride (CCl4) can cause acute hepato-renal injury by producing free radicals and inflammatory mediators. Therefore, we examined the impact of glutamine (Gln) on oxidative stress and inflammatory markers in blood and tissue homogenates, as well as hepato-renal dysfunction markers and histopathological parameters in an oxidative stress rat model induced by CCl₄.

The study included four groups, each comprising nine rats: control (C), oxidative stress rat model (OSRM), and those treated with Gln (1,000 mg/L in drinking water for 2 weeks). Oxidative stress was induced by administering CCl₄ (1 ml/kg) on the 15^th day. The hepatic NF-kβ expression was analyzed, and markers of oxidative stress and inflammation were assessed. Additionally, biochemical markers of hepatic and renal functions were measured, and histopathological changes in the liver and kidney tissues were examined.

The findings indicated that Gln treatment significantly reduced liver and kidney histopathological changes caused by oxidative stress induction. The treatment lowered hepatic NF-kβ expression, liver and renal dysfunction parameters, and markers of oxidative stress and inflammation. Moreover, it notably improved systemic, renal, and hepatic antioxidant potential (P < 0.001).

The hepato-renoprotective effects of Gln included the prevention of liver necrosis and renal tubule disturbance. Gln enhanced liver and kidney functions by reducing NF-kβ signaling and boosting systemic, hepatic, and renal antioxidant potential through elevating the glutathione (GSH)/GSSG ratio and antioxidant enzyme activities. It is likely that the enhancement of the glutamine-glutathione axis is the primary mechanism behind its hepato-renoprotective effects.