Premium
Renoprotective effect of Hypericum perforatum against diabetic nephropathy in rats: Insights in the underlying mechanisms
Author(s) -
Abd El Motteleb Dalia M.,
Abd El Aleem Dalia I.
Publication year - 2017
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/1440-1681.12729
Subject(s) - endocrinology , gliclazide , medicine , diabetic nephropathy , oxidative stress , chemistry , malondialdehyde , nitric oxide synthase , superoxide dismutase , streptozotocin , creatinine , nitric oxide , pharmacology , diabetes mellitus
Summary Oxidative stress and inflammation play a key role in the initiation and progression of diabetic nephropathy ( DN ). The present study aimed to investigate the possible protective effect of hypericum perforatum ( HP ) against DN . Rats were allocated into six groups: control, received normal saline; diabetic untreated ( DM ), received single dose of streptozotocin ( STZ ) after injection of nicotinamide ( NA ); gliclazide, received STZ , NA + gliclazide (10 mg/kg); DM + HP 50, DM + HP 100, DM + HP 200, received STZ , NA and HP 50, 100, 200 mg/kg, respectively. Gliclazide and HP were administered daily via gavage for 8 weeks. Serum glucose, insulin, kidney function and histopathological picture were assessed. Furthermore, oxidative/nitrosative stress, inflammatory cytokines, apoptotic and fibrotic markers were measured. Diabetic untreated group showed increase in serum glucose, urea, creatinine with albuminurea. Renal expression of protein for nuclear factor kappa‐B ( NF ‐кB), renal expression of inducible nitric oxide synthase ( iNOS ), cyclooxygenase II ( COXII ), collagen IV , fibronectin were elevated. Malondialdehyde ( MDA ), nitric oxide ( NO ), tumour necrosis factor‐α ( TNF ‐α), interleukin‐1β ( IL ‐1β), intracellular adhesion molecule ( ICAM ‐1), monocellular chemoattractant protein‐1 ( MCP ‐1), tumour growth factor‐ β ( TGF ‐β), caspase‐3 and cytochrome c contents were also increased consequently with decline of serum insulin, expression of peroxisome proliferator‐activated receptor ( PPAR γ), renal reduced glutathione ( GSH ) content and superoxide dismutase ( SOD ) activity. Treatment with either gliclazide or HP mitigated the deleterious effects of STZ on the tested parameters. These findings indicate for the first time that HP may have a renoprotective effect against DN through reduction of oxidative/nitrosative stress, enhancement of antioxidant defense mechanisms, decline of inflammatory cytokines, antifibrotic, antiapoptotic and blood glucose lowering properties.