Effect of chronic excess iodine intake on thyroid function and oxidative stress in hypothyroid rats.

Our objective was to investigate the effects of chronic excess iodine intake on thyroid functions and thyroid oxidative stress state in hypothyroid rats. Sixty rats were divided into euthyroid and hypothyroid (thiocyanate-induced) groups with or without administration of excess iodine (3000 or 6000 µg/L) for 8 weeks. Serum thyroxine (T(4)), triiodothyronine (T(3)), thyroid-stimulating hormone (TSH), thyroid antioxidants (catalase, superoxide dismutase enzymes, and total antioxidants), and lipid peroxide (malondialdehyde; MDA) were measured. Reverse transcription - PCR gene expression for thyroidal Na(+)/I(-) symporter (NIS), D1 deiodinase, and thyroid peroxidase (TPO) were performed. Thiocyanate significantly decreased thyroid hormones (T(3), T(4)), increased lipid peroxides and antioxidants, and increased gene expression of NIS, D1 deiodinase, and TPO. Excess iodine intake in hypothyroid rats increased T3 and T4. Also, high iodine intake by hypothyroid rats significantly decreased NIS, D1 deiodinase, and TPO genes expression. Excess iodine significantly increased MDA and antioxidants in euthyroid and hypothyroid rats. In conclusion, thiocyanate-hypothyroidism increases gene expression of NIS, TPO, and TPO and induces oxidative stress. High iodine intake decreases NIS and D1 deiodinase gene expression in hypothyroid rats. Moreover, excess iodine increase thyroid hormones, lipid peroxides, and antioxidants in hypothyroid rats.

Modulation of metabolic and cardiac dysfunctions by insulin sensitizers and angiotensin receptor blocker in rat model of type 2 diabetes mellitus.

The objective of this study was to investigate the modulation of metabolic dysfunctions, adiponectin levels, and cardiac dysfunctions of type 2 diabetes mellitus (T2DM) by a combination of the insulin sensitizer rosiglitazone and angiotensin receptor blocker telmisartan in an experimental rat model. Fifty male adult Sprague-Dawley rats were divided equally into 5 groups. Group I: fed normal chow; served as normal control group. Groups II-V: fed a high-fat diet (HFD) for 2 weeks, followed by injection of streptozotocin (STZ; 35 mg/kg) to create a model of T2DM. Group II: treated with vehicle. Group III: treated with rosiglitazone (4 mg/kg). Group IV: treated with telmisartan (5 mg/kg). Group V: treated with both agents. Untreated HFD-STZ rats showed elevated fasting blood glucose, insulin, homeostasis model assessment (HOMA) index, triglycerides (TGs), low-density lipoprotein cholesterol (LDL), and total serum cholesterol (TC), with a decrease in high-density lipoprotein cholesterol (HDL) and adiponectin levels (p < 0.001). Rosiglitazone exerted more improvement in all parameters than telmisartan did, and a combination of both did not augment the improvement further, except for TGs and adiponectin. For the isolated atrial study, a combination of rosiglitazone and telmisartan corrected the responses of the atria of HFD-STZ rats to the negative inotropic effect induced by adenosine better than either one did alone, whereas this combination, surprisingly, significantly attenuated the positive inotropic response to ß-adrenoreceptor and α-adrenoreceptor agonists. In conclusion, rosiglitazone significantly improved the metabolic and cardiac dysfunctions in T2DM. Moreover, a combination of rosiglitazone and telmisartan offered more improvement in serum TGs and adiponectin, and restored the atrial inotropic response to adenosine. Surprisingly, this combination significantly attenuates the positive inotropic response to α1-adrenoreceptor and ß-adrenoreceptor agonists.

Effects of combined erythropoietin and epidermal growth factor on renal ischaemia/reperfusion injury: a randomized experimental controlled study.

OBJECTIVE: To investigate effects of combination of erythropoietin (EPO) and epidermal growth factor (EGF) on renal ischaemia and on reactive oxygen species in a rat model. MATERIALS AND METHODS: In all, 90 male Sprague-Dawley rats were allocated into five groups of 18, designated: Sham; treated with right nephrectomy only; Control, subjected to left renal ischaemia for 45 min with no treatment; EPO-treated, as the control but with EPO pretreatment; EGF-treated, as the control but with EGF pretreatment; EPO + EGF-treated, as the control but with EPO and EGF pretreatment. Renal function, histopathology and malondialdehyde (MDA), superoxide dismutase (SOD) and reduced glutathione (GSH) levels in kidneys were assessed at 1, 2 and 7 days after ischaemia. RESULTS: All rats except the controls had a significant improvement in serum creatinine, creatinine clearance and fractional excretion of Na(+) ; all three were significantly better in EPO + EGF group than in all other groups Histopathological examination showed marked structural damage in control rats. The tubular damage was least in the EPO + EGF group. The control group had a significant increase in MDA level and a significant decrease in SOD and GSH, while the EPO + EGF group had a marked significant reduction in MDA and increase in GSH and SOD. CONCLUSION: The protection against ischaemia/reperfusion injury might be maximal when EPO and EGF are administered concomitantly, and their protective effect might be partly due to their antioxidant effects.

Role of combined L-arginine and prostaglandin E1 in renal ischemia-reperfusion injury.

BACKGROUND: L-Arginine (L-arg) and Prostaglandin E(1) (PGE(1)) have been used effectively as single agents to ameliorate renal ischemia-reperfusion injury. We hypothesized that combined treatment with L-arg and PGE(1 )would be more effective. MATERIALS AND METHODS: The left renal artery of male Sprague-Dawley rats was clamped for 45 min and the right kidney was removed. Fifty six rats were randomly allocated into 5 groups each consisted of 12 rats except sham group (n = 8). (1) sham, underwent right nephrectomy only; (2) control, untreated ischemic rats; (3) L-arg group, L-arg-treated ischemic rats; (4) PGE(1) group, PGE(1)-treated ischemic rats; (5) L-arg+PGE(1) group, ischemic rats treated with both L-arg and PGE(1). Renal function and histology were assessed on days 2 and 7 postoperatively. RESULTS: All rats, except control ones, showed a significant improvement of renal function towards normal on postoperative day 7. Serum creatinine and creatinine clearance were significantly better in L-arg+PGE(1) group compared to all other groups on day 7. With the exception of sham-operated and L-arg+PGE(1)-treated animals, all other groups showed significant increases in fractional excretion of sodium (FE(Na)) in response to renal ischemia-reperfusion. The severest tubular damage was determined in the kidneys of control rats. Rats treated with L-arg+PGE(1) had the least severe tubular damage. CONCLUSION: The administration of either L-arg or PGE(1) attenuates both functional and structural consequences of renal warm ischemia. A near total protection might be achieved when both agents are administered concomitantly.