Ameliorative effect of papain supplementation on renal tissue bioenergetic, redox and inflammatory alterations and Ppargc1a/PGC-1α mRNA expression in fructose/streptozotocin-induced diabetic rats

Abstract Background Diabetic kidney injury is associated with renal bioenergetic disturbance, redox imbalance and impaired mitochondrial biogenesis signalling. This study evaluated whether papain supplementation attenuates renal bioenergetic, redox and inflammatory alterations and modulates Ppargc1a/PGC-1α mRNA expression in fructose/streptozotocin-induced diabetic rats. Twenty-five male Wistar rats ( n = 5/group) were assigned to five groups: non-diabetic control, diabetic only, high-dose papain (800 mg/kg/day), low-dose papain (400 mg/kg/day) and metformin (100 mg/kg/day), the last three on a diabetic background. After 28 days, renal tissue was analysed for injury-associated analytes, bioenergetic and antioxidant markers, inflammatory cytokines and Ppargc1a/PGC-1α mRNA expression. Data were analysed by one-way ANOVA with Bonferroni post hoc test ( p < 0.05). Results In the oral glucose tolerance test, both papain doses restored the glycaemic excursion and area under the curve to near-control values, with no clear dose separation and with tighter control than metformin; both papain groups were also protected from the progressive body-weight gain and hyperphagia of the untreated diabetic group. At the renal level, diabetes significantly increased creatinine, urea, lactate, pyruvate and tumour necrosis factor alpha and reduced succinate dehydrogenase, glutathione, interleukin 10 and Ppargc1a/PGC-1α mRNA, while high-dose papain significantly improved these endpoints relative to the diabetic group; low-dose papain produced a weaker response, and metformin showed similar recovery. Conclusions Papain supplementation improved renal bioenergetic and antioxidant markers, rebalanced inflammatory cytokines and up-regulated Ppargc1a/PGC-1α mRNA expression, performing comparably to or better than metformin and supporting papain as a promising renoprotective candidate in diabetic kidney disease.