Department of Pharmacology, Faculty of Medicine, Suez Canal University, Ismailia, Egypt.
Eur Rev Med Pharmacol Sci. 2009 Nov-Dec;13(6):443-51.
The present study was conducted to assess the effect of Pioglitazone, an oral antidiabetic drug with selective PPAR-gamma agonist effect; in a dose of 4 mg/kg B.W. once a day orally for eight weeks on the liver of streptozotocin-induced diabetic rats.
Sixty male adult albino Wistar rats were equally randomly into six groups (n=10). Group I: normal control group was received no medication. Group II: distilled water control group, they are non diabetic group and received distilled water once a day orally by gastric tube for 8 weeks. Group III: citrate buffer control group, they are non diabetic received a single intraperitoneal injection of an equivalent amount of vehicle (citrate buffer, pH 4.5) 1 ml/kg at the time of induction. Group IV: Pioglitazone control group, they are non diabetic received pioglitazone HCl, single dose of 4 mg/kg b.w. once a day orally by gastric tube for eight weeks. Group V: diabetic control group, they are streptozotocin-induced diabetic rats that received no medication. Group VI: diabetic treated group, they are streptozotocin-induced diabetic rats treated by pioglitazone for eight weeks.
At the end of the experiment microscopic examination of the liver sections in the diabetic control group, showed mild to moderate portal inflammatory infiltrate, mostly lymphocytic as well as intralobular cell necrosis and apoptosis as well as bile stasis. These results were associated serologically with elevation of all liver parameters. Pioglitazone administration in the normal rats for eight weeks didn't show any significant difference neither serologically nor histopathologically compared with normal control group. Moreover, pioglitazone administration caused statistically significant reduction in the mean levels of liver tests, as well as fasting blood glucose of the STZ-induced diabetic rats.
There is no evidence that pioglitazone administration has a harmful effect on the liver. On the other hand, it has a potential beneficial effects on the liver during treatment of STZ-induced diabetic rats, suggesting that liver toxicity isn't a class effect of the thiazolidinediones but rather a unique effect of troglitazone.
本研究旨在评估吡格列酮(一种具有选择性 PPAR-γ激动剂作用的口服抗糖尿病药物)的作用,以 4mg/kgBW 每天口服一次的剂量连续八周治疗链脲佐菌素诱导的糖尿病大鼠的肝脏。
60 只雄性成年白化 Wistar 大鼠被平均随机分为六组(n=10)。第 I 组:正常对照组未接受任何药物治疗。第 II 组:蒸馏水对照组,非糖尿病组,每天通过胃管给予蒸馏水 1ml/kg,连续 8 周。第 III 组:柠檬酸缓冲液对照组,非糖尿病组,在诱导时给予等体积的载体(柠檬酸缓冲液,pH4.5)1ml/kg 单次腹腔内注射。第 IV 组:吡格列酮对照组,非糖尿病组,给予盐酸吡格列酮,单次剂量 4mg/kgBW,每天通过胃管口服,连续 8 周。第 V 组:糖尿病对照组,未接受任何药物治疗的链脲佐菌素诱导的糖尿病大鼠。第 VI 组:糖尿病治疗组,接受吡格列酮治疗 8 周的链脲佐菌素诱导的糖尿病大鼠。
实验结束时,糖尿病对照组的肝组织切片镜检显示轻度至中度门脉炎症浸润,主要为淋巴细胞,以及小叶内细胞坏死和凋亡以及胆汁淤积。这些结果与血清学检查中所有肝参数的升高相关。吡格列酮在正常大鼠中连续 8 周给药,与正常对照组相比,无论是血清学还是组织病理学均无显著差异。此外,吡格列酮给药可使 STZ 诱导的糖尿病大鼠的肝试验均值水平以及空腹血糖显著降低。
没有证据表明吡格列酮给药对肝脏有有害影响。另一方面,它对治疗 STZ 诱导的糖尿病大鼠的肝脏具有潜在的有益作用,这表明肝毒性不是噻唑烷二酮类的类效应,而是曲格列酮的独特效应。