title: Ginsenoside-Rb1 ameliorates lithium-induced nephrotoxicity and neurotoxicity: Differential regulation of COX-2/PGE2pathway.
abstract: To investigate the effect of Ginsenoside-Rb1 (GRb1) on lithium (Li+)-induced toxicity, GRb1 was given to rats orally (100mg/kg) for 14days. In independent groups, lithium chloride (4meq/kg/day i.p.) was administered at day 4 of the experiment for 10days, with or without GRb1. Li+caused significant deterioration of behavioral responses including righting reflex, spontaneous motor activity and catalepsy. Li+also caused distortion in normal renal, cerebral and cerebellum architecture and significantly worsened all kidney functional parameters tested compared to control. In addition, Li caused oxidative stress in both kidney and brain, evident by significant increase in malondialdehyde and nitric oxide levels, with decrease in reduced glutathione and catalase activity. Administration of GRb1 prior to Li+significantly improved behavioral responses, renal and brain histopathological picture, kidney function tests and oxidative stress markers compared to sole Li+-treated group. Concomitant administration of GRb1 decreased Li+levels by about 50% in serum, urine and brain and by 35% in the kidney. Interestingly, Li+had a differential effect on cyclooxygenase (COX)-2/prostaglandin E2(PGE2) pathway, as it significantly increased COX-2 expression and PGE2level in the kidney, while decreasing them in the brain compared to control. On the other hand, administering GRb1 with Li+suppressed COX-2/PGE2pathway in both kidney and brain compared to Li+alone. In conclusion, GRb1 can alter Li+pharmacokinetics resulting in extensively decreasing its serum and tissue concentrations. Furthermore, COX-2/PGE2pathway has a mechanistic role in the nephro- and neuro-protective effects of GRb1 against Li+-induced toxicity.
authors.affiliation: Pharmacology Department, Faculty of Medicine, Minia University, Egypt. Electronic address: azza.elsheikh@mu.edu.eg.
authors.forename: Azza A K
authors.initials: AAK
authors.lastname: El-Sheikh
authors.affiliation: Pharmacology Department, Faculty of Medicine, Minia University, Egypt.
authors.forename: Maha Y
authors.initials: MY
authors.lastname: Kamel
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D015232:Dinoprostone / Q000037:antagonists & inhibitors / Q000378:metabolism*; D036145:Ginsenosides / Q000302:isolation & purification / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D018021:Lithium Chloride / Q000037:antagonists & inhibitors / Q000633:toxicity*; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D005894:Panax; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
chemical_list: D036145:Ginsenosides; C442759:ginsenoside Rb1; D051546:Cyclooxygenase 2; D018021:Lithium Chloride; D015232:Dinoprostone
keywords: Cyclooxygenase-2; Ginsenoside Rb1 (PubChem CID: 9898279); Ginsenoside rb1; Lithium; Lithium chloride (PubChem CID: 433294); Nephrotoxicity; Neurotoxicity; Prostaglandin E(2)