Naringin corrects renal failure related to Lesch-Nyhan disease in a rat model via NOS-cAMP-PKA and BDNF/TrkB pathways.

This study explored the effect of naringin (NAR) on HGPRT1 deficiency and hyperuricemia through NOS-cAMP-PKA and BDNF/TrkB signaling pathways induced by caffeine (CAF) and KBrO in a rat model. Sixty-three adult male albino rats were randomly assigned into nine (n = 7) groups. Group I: control animals, Group II was treated with 100 mg/kg KBrO , Group III was treated with 250 mg/kg CAF, Group IV was treated with 100 mg/kg KBrO  + 250 mg/kg CAF, Group V was administered with 100 mg/kg KBrO  + 100 mg/kg haloperidol, Group VI was administered with 100 mg/kg KBrO  + 50 mg/kg NAR, Group VII was administered with 500 mg/kg CAF + 50 mg/kg NAR, and Group VIII was administered with 100 mg/kg KBrO  + 250 mg/kg CAF + 50 mg/kg NAR. Finally, group IX was treated with 50 mg/kg NAR. The exposure of rats to KBrO and CAF for 21 days induced renal dysfunction linked with Lesch-Nyhan disease. NAR obliterated renal dysfunction linked with Lesch-Nyhan disease by decreasing uric acid, renal malondialdehyde level, inhibiting the activities of arginase, and phosphodiesterase-5 (PDE-51) with corresponding upregulation of brain derived-neurotrophic factor and its receptor (BDNF-TrkB), Bcl11b, HGPRT1, and DARPP-32. Additionally, renal failure related to Lesch-Nyhan disease was remarkably corrected by NAR as shown by the reduced activities of AChE and enzymes of ATP hydrolysis (ATPase, AMPase, and ADA) with affiliated increase in the NO level. This study therefore validates NAR as nontoxic and effective chemotherapy against kidney-related Lesch-Nyhan disease by mitigating effects of toxic food additives and enzymes of ATP-hydrolysis via NOS-cAMP-PKA and BDNF/TrkB signaling pathways.