Learning and memory disorders in impaired striatum lack sufficient HGPRTI on exposure to caffeine and KBr03, whereas its chemotherapeutic treatment with naringenin-7-O-neohesperidoside was elicited via NOS/cAMP/PKA and BDNF/TrkB signaling responses

Abstract

• Mixture of caffeine and KBrO 3 causes vasoconstriction injury. • It also promotes striatum limbic neurotransmitter enzymes. • It also exerts the symptoms of Lesch-Nyhan-Syndrome (LNS) • Naringenin-7-O-neohesperidoside inhibits vasoconstriction injury. • It depletes the indicators of LNS in an in-vivo model. This study investigated the chemotherapeutic efficacy of naringenin-7-O-neohesperidoside (NAR) against Lesch-Nyhan syndrome and neurobehavioral abnormalities in rat models. Ninety male Wistar rats were grouped into nine groups (n = 10). Group I: control rats, Group II was exposed to 100 mg/kg KBrO 3 , Group III was exposed to 250 mg/kg CAF, Group IV was exposed to 100 mg/kg KBrO 3 + 250 mg/kg CAF. Group V was administered with 100 mg/kg KBrO 3 + 100 mg/kg HAL. Group VI was administered with 100 mg/kg KBrO 3 + 50 mg/kg NAR. Group VII was administered with 250 mg/kg CAF + 50 mg/kg NAR. Group VIII was treated with 100 mg/kg KBrO 3 + 250 mg/kg CAF + 50 mg/kg NAR. Finally, group IX was treated with 50 mg/kg NAR. The study lasted for five weeks. The result showed that striatal hypoxanthine–guanine-phosphoribosyl transferase-1 (HGPRT1) was suppressed on exposure to KBrO 3 only, CAF only and KBrO 3 + CAF by 52.5% when compared with the control. The post-administration with NAR remarkably elevated the expression of striatal HGPRT1 in relation to the corresponding exposed groups by 22.8%, 31.6%, 40.4% and 14.0%, respectively. NAR also inhibited the activities of arginase and phosphodiesterase-5 1 (PDE-5 1 ) with corresponding up-regulation of dopamine and cAMP-regulated-phosphoprotein (DARPP), brain-derived neurotrophic factor (BDNF), and tropomyosin-receptor-kinase-B (TrkB). Similarly, the gene coding for B-cell lymphoma/leukaemia 11b (Bcl11b) was down-regulated. Additionally, NAR remarkably reduced the activities of AChE, BuChE, MAO-A and enzymes of ATP hydrolysis (ATPase, AMPase and ADA) with consequential increase in NO level. Also, locomotion, coordination, and memory were improved upon post-treatment with NAR, followed by repression of self-mutilation, anxiety and depression. Also, vascular congestion of nigrostriatal tracts, cellular degeneration of striatum, plasma uric-acid and malonaldehyde (MDA) contents were essentially lowered. This study proposes that NAR could be a viable therapeutic agent for the up-regulation of striatal-HGPRTI-gene to inhibit Lesch-Nyhan Syndrome and neurobehavioral abnormalities through NOS/cAMP/PKA and BDNF/TrkB signalling cascades in a rat model