Effects of nicorandil on vascular and renal dysfunctions in adenine-induced nephropathy: Possible underlying mechanisms.

Vascular dysfunctions in chronic kidney disease (CKD) include endothelial dysfunctions and vascular calcification (VC). In the present study, we examined the possible protective effect of nicorandil (potassium channel opener) on renal and vascular dysfunctions in a rat model of adenine-induced nephropathy and its underlying mechanisms. Thirty-four male Sprague-Dawley rats were randomly allocated into 3 groups: Control group, Adenine group (animals received high-adenine diet for 4 weeks), and Nicorandil group (animals received adenine for 4 weeks and nicorandil 1 mg/kg per oral for 4 weeks). The results showed significant reduction in the body weight, heart rate (HR), hemoglobin contents, serum Ca2+ and reduction in the expression of mRNA of endothelial nitric oxide synthase (eNOS) and nuclear factor erythroid related factor 2 (nrf2) genes in aortic tissues with significant increase in arterial blood pressure (ABP), serum creatinine, blood urea nitrogen (BUN), plasma renin activity (PRA), K+ and phosphate (PO43-), urinary albumin excretion (UAE) and aortic VC in Adenine group compared to normal group (p < 0.05). On the other hand, coadminsitration of nicorandil caused significant improvement in the studied parameters compared to Adenine group (p < 0.05). We concluded that nicorandil has a potential protective effect against the vascular and renal impairment induced by adenine, which might be due to attenuation of vascular calcifications, activation of Nrf2 and eNOS genes in aortic tissues.

Effect of peroxisome proliferator-activated receptor gamma agonist (pioglitazone) and methotrexate on disease activity in rheumatoid arthritis (experimental and clinical study).

OBJECTIVE: To investigate the combined effect of both pioglitazone and methotrexate on disease activity of rheumatoid arthritis in a biphasic study; experimental and clinical. METHODS: EXPERIMENTALLY: 50 rats were divided into 5 equal groups; controls, experimental arthritis, methorexate treated (0.1 mg/Kg daily), pioglitazone-treated (10 mg/kg daily), and methotrexate and pioglitazone treated. Clinically: forty-nine diabetic rheumatoid arthritis patients were included. Patients group consisted of 28 patients and they received pioglitazone 30 mg orally beside their usual treatment. Control group consisted of 21 patients and they continued their usual treatment plus placebo. Disease activity was assessed using DAS28 score. Patients were followed up for 3 months. RESULTS: Pioglitazone produced a significant improvement of serum oxidative stress parameters (P < 0.05), and inflammatory cytokines in the treated arthritic group (P < 0.05). Clinically, the pioglitazone treated group showed significant improvement in DAS28 (P = 0.001) and C-reactive protein (P < 0.0001) compared to placebo group. CONCLUSION: The concomitant use of the PPAR γ agonist pioglitazone and methotrexate appears to be promising therapeutic strategy for rheumatoid arthritis patients.