Essam Fouad Aly

Objective: to explore allopurinol action on the metabolic syndrome (MS) components induced by high fructose diet (HFD). Material & methods: Twenty-one rats were classified randomly into 2 groups; group A (7 rats; normal control) and group B (14 rats; received a high fructose diet (HFD). Meanwhile, group B is further classified into 2 subgroups: B1 received no treatment and B2 in which rats received allopurinol (4mg/kg/d for 4 weeks). Results: Allopurinol significantly decreased body weight (BW), normalized kidneys and heart weight, blood pressure (BP) and insulin level with normalized both of fasting glucose level and insulin resistance (IR). Furthermore, triglycerides (TGs) and low-density lipoprotein cholesterol (LDL-c) were significantly decreased with normalized high-density lipoprotein cholesterol (HDL-c), total cholesterol, creatinine, blood urea nitrogen (BUN), and serum uric acid (SUA) levels. Surprisingly, allopurinol significantly up regulate adiponectin receptor one and two (adipo R1/R2) and heme oxygenase-1 (HO-1) in heart, liver and kidneys pancreas associated with up regulation of endothelial nitric oxide synthase (eNOS) expression in liver, kidneys, heart only associating with amelioration of the fibrotic changes in different tissue studied. Moreover, it normalized IR, pancreatic AdipoR2, and HO-1 expression. Conclusion: allopurinol could be considered an ideal agent for an amelioration of MS components possibly through up regulation of adipo R1/R2, HO-1 and eNOS in different tissues; however more experimental and clinical studies are needed to weight the expected allopurinol benefit against its long term use related side effects

Metabolic syndrome (MS) is a cluster of hypertension, insulin resistance, dyslipidaemia, and hyperuricemia. This study was designed to assess the effect of telmisartan and pioglitazone on high fructose induced MS. Thirty-five male albino rats were classified into 5 groups: A, normal diet; B, high-fructose diet (HFD) subdivided into B1 (HFD only), B2 (telmisartan, 5 mg/kg), B3 (pioglitazone, 10 mg/kg), and B4 (telmisartan + pioglitazone). Administration of the drugs was started after the rats had been on HFD for 4 weeks and continued for 4 weeks. Body mass (BM), blood pressure (BP), uric acid (UA), total cholesterol, triglycerides (TG), high-density lipoprotein (HDL-c), low-density lipoprotein (LDL-c), blood urea nitrogen (BUN), creatinine, and nitric oxide (NO) were measured and the levels of fasting glucose and fasting insulin were estimated. Compared with group B1, telmisartan treatment significantly decreased BP, BM, serum glucose, insulin, UA, urea, cholesterol, TGA, and LDL and significantly increased HDL, whereas pioglitazone treatment significantly decreased BP, serum glucose, insulin, UA, urea, creatinine, cholesterol, TGA, and LDL and significantly increased HDL. Co-administration of pioglitazone + telmisartan significantly decreased insulin, urea, and creatinine compared with telmisartan alone. Combined telmisartan + pioglitazone allowed better control of BP, hyperglycaemia, insulin resistance, and the amelioration of BM increase that may be associated with pioglitazone treatment.

Hepatic schistosomiasis is considered to be one of the most prevalent forms of chronic liver disease in the world due to its complication of liver fibrosis. The demonstration of the pro-fibrogenic role of angiotensin (Ang) II in chronic liver disease brought up the idea that anti-Ang II agents may be effective in improving hepatic fibrosis by either blocking Ang II type 1 (AT1) receptors or inhibiting the angiotensin converting enzyme. Peroxisome proliferator-activated receptors gamma (PPARγ) activation has been also shown to inhibit hepatic stellate cell activation and progression of fibrosis. The present study has aimed at testing the anti-fibrogenic effects of telmisartan; an AT1 receptor blocker and a PPARγ partial agonist, alone or combined with praziquantel (PZQ) on Schistosoma mansoni-induced liver fibrosis in mice.
METHODS:
To achieve the aim of the study, two sets of experiments were performed in which telmisartan was initiated at the 5th (set 1) and the 10th (set 2) weeks post infection to assess drug efficacy in both acute and chronic stages of liver fibrosis, respectively. Schistosoma mansoni-infected mice were randomly divided into the following four groups: infected-control (I), telmisartan-treated (II), PZQ-treated (III), and telmisartan+PZQ-treated (IV). In addition, a normal non-infected group was used for comparison. Parasitological (hepatomesenteric worm load and oogram pattern), histopathological, morphometric, immunohistochemical (hepatic expressions of matrix metalloproteinase-2; MMP-2 and tissue inhibitor of metalloproteinase-2; TIMP-2), and biochemical (serum transforming growth factor beta 1; TGF-β1 and liver function tests) studies were performed.
RESULTS:
Telmisartan failed to improve the parasitological parameters, while it significantly (P<0.05) decreased the mean granuloma diameter, area of fibrosis, and serum TGF-β1. Additionally, telmisartan increased MMP-2 and decreased TIMP-2 hepatic expression. Combined treatment failed to show any additive properties, yet it did not affect the anti-schistosomal activity of PZQ.
CONCLUSIONS:
These results suggest potential anti-fibrotic effects of telmisartan, an AT1 receptor blocker and a PPARγ partial agonist, in acute and chronic stages of Schistosoma mansoni-induced liver fibrosis in mice.