PMID- 28079268 OWN - NLM STAT- MEDLINE DCOM- 20170710 LR - 20170713 IS - 1440-1681 (Electronic) IS - 0305-1870 (Linking) VI - 44 IP - 4 DP - 2017 Apr TI - Renoprotective effect of Hypericum perforatum against diabetic nephropathy in rats: Insights in the underlying mechanisms. PG - 509-521 LID - 10.1111/1440-1681.12729 [doi] AB - 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 + HP50, DM + HP100, DM + HP200, 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-small ka, CyrillicB), renal expression of inducible nitric oxide synthase (iNOS), cyclooxygenase II (COXII), collagen IV, fibronectin were elevated. Malondialdehyde (MDA), nitric oxide (NO), tumour necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), intracellular adhesion molecule (ICAM-1), monocellular chemoattractant protein-1 (MCP-1), tumour growth factor- beta (TGF-beta), caspase-3 and cytochrome c contents were also increased consequently with decline of serum insulin, expression of peroxisome proliferator-activated receptor (PPARgamma), 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. CI - (c) 2017 John Wiley & Sons Australia, Ltd. FAU - Abd El Motteleb, Dalia M AU - Abd El Motteleb DM AUID- ORCID: 0000-0002-4379-6323 AD - Department of Pharmacology, Faculty of Medicine, Zagazig University, Zagazig, Egypt. FAU - Abd El Aleem, Dalia I AU - Abd El Aleem DI AD - Department of Medical Physiology, Faculty of Medicine, Zagazig University, Zagazig, Egypt. LA - eng PT - Journal Article PL - Australia TA - Clin Exp Pharmacol Physiol JT - Clinical and experimental pharmacology & physiology JID - 0425076 RN - 0 (Antioxidants) RN - 0 (Collagen Type IV) RN - 0 (Fibronectins) RN - 0 (Inflammation Mediators) RN - 0 (NF-kappa B) RN - 0 (PPAR gamma) RN - 0 (Transforming Growth Factor beta) RN - EC 1.14.13.39 (Nitric Oxide Synthase Type II) RN - EC 1.14.99.1 (Cyclooxygenase 2) RN - G4PX8C4HKV (Gliclazide) SB - IM MH - Animals MH - Antioxidants/metabolism MH - Apoptosis/drug effects MH - Body Weight/drug effects MH - Collagen Type IV/metabolism MH - Cyclooxygenase 2/metabolism MH - *Cytoprotection/drug effects MH - Diabetic Nephropathies/*metabolism/*pathology MH - Fibronectins/metabolism MH - Gene Expression Regulation, Enzymologic/drug effects MH - Gliclazide/pharmacology MH - Hypericum/*physiology MH - Inflammation Mediators/metabolism MH - Kidney/drug effects/metabolism/*pathology MH - Male MH - NF-kappa B/metabolism MH - Nitric Oxide Synthase Type II/metabolism MH - Oxidative Stress/drug effects MH - PPAR gamma/metabolism MH - Rats MH - Rats, Wistar MH - Transforming Growth Factor beta/metabolism OTO - NOTNLM OT - hypericum perforatum OT - NF-small ka, CyrillicB OT - PPAR gamma OT - TGF-beta OT - diabetic nephropathy OT - gliclazide OT - oxidative stress EDAT- 2017/01/13 06:00 MHDA- 2017/07/14 06:00 CRDT- 2017/01/13 06:00 PHST- 2016/05/21 00:00 [received] PHST- 2016/12/30 00:00 [revised] PHST- 2017/01/04 00:00 [accepted] PHST- 2017/01/13 06:00 [pubmed] PHST- 2017/07/14 06:00 [medline] PHST- 2017/01/13 06:00 [entrez] AID - 10.1111/1440-1681.12729 [doi] PST - ppublish SO - Clin Exp Pharmacol Physiol. 2017 Apr;44(4):509-521. doi: 10.1111/1440-1681.12729.