Objective(s): PIOGLITAZONE (Actos) is one of the most controversial recent oral antidiabetic drugs. It was originally authorized in the European Union in 2000, and approved as an oral monotherapy for overweight second type of diabetic patients in 2002. It belongs to the thiazolidinedione group which some of its members have been withdrawn from the market due to the hepatotoxicity or cardiotoxicity effects. This study investigates sub-chronic use of PIOGLITAZONE induced toxicity in mice by the assessment of renal and liver function tests, cardiac enzymes, and some hematological indices with histological changes of liver, kidney, heart, and bladder. Materials and Methods: 120 albino mice were divided into four groups; 30 in each. The first group (control) received water, second (diabetic) group received alloxan only, while the third and the fourth groups received alloxan with 200 and 400 mg/kg/day of PIOGLITAZONE, respectively for 90 days. Results: Prolonged use of PIOGLITAZONE induced significant abnormalities of hepatic, renal, and cardiac biomarkers and some hematological indices associated with histopathological changes in the liver, kidney, heart, and bladder that increased based on administered dose. Conclusion: Subchronic use of PIOGLITAZONE leads to hepatic, renal, cardiac, hematological, and bladder affection depending on the applied dose.

Solubility is an important physicochemical factor for any drug molecule that affects its absorption along with its therapeutic effectiveness. Drug absorption is predominantly dependent upon its prompt dissolution. In the case of poorly water-soluble drugs, dissolution is the rate-limiting step in the process of drug absorption. Microspheres were prepared by solvent evaporation method using polymers namely Eudragit L100 and Eudragit RL100. Direct compression technique was used for the preparation of tablets. Tablets were prepared with MCC and PVP K-30 as polymers using an 8 mm punch on a rotary press machine with a constant force. Microspheres and the prepared tablets were evaluated using various evaluation tests. The prepared microspheres showed >80% entrapment efficiency and percent yield. Batch F3 exhibited the highest drug release up to 98. 30%. Fourier transform infrared (FT-IR) studies revealed no drug– polymer interaction. The results of SEM exhibited that the microspheres are spherical in shape with an average size 5µ m. The result of all batches was within an acceptable limit. F2 batch tablet showed a higher drug release of 98. 30% as compared with other batches. It was concluded that microcrystalline cellulose or PVP K-30, when used separately, caused retardation in drug release, whereas when used in combination (1: 1) it achieved drug release in a controlled manner.

Background: Epilepsy is a neurological disorder caused by uncontrollable discharge of action potentials from neurons in the brain. After a seizure, oxidative stress may cause a significant neuronal damage. In the current study, we assessed the anticonvulsant and antioxidant properties of PIOGLITAZONE, a peroxisome proliferated activated receptor-γ,(PPAR-γ, ) agonist that is used in type-2 diabetes, on pilocarpine-induced seizure in mice. Methods: Pilocarpine (400 mg/kg) or normal saline was injected intraperitoneally 4 hours after oral administration of PIOGLITAZONE (80 mg/kg). Also, carboxymethyl cellulose was administered orally in control and Pilocarpine groups. After the administration of Pilocarpine all of the mice were observed for 1 hour to measure the seizure latency time. Pilocarpineinduced seizures were categorized using the Racine scale. Then all animals were decapitated, brain was removed and hippocampus was dissected. Finally, the level of Malondialdehyde (MDA) and Catalase (CAT) activity, Superoxide Dismutase (SOD), and Glutathione Reductase (GR) levels were quantified in hippocampus by biochemical methods. Results: PIOGLITAZONE significantly increased the latency to seizure onset of stages 1-4 (P≤, 0. 01-0. 001). Also, PIOGLITAZONE prevented the development of stage 5 of the pilocarpine-induced seizure. After the seizure, PIOGLITAZONE significantly decreased the level of MDA (P<0. 01) and elevated the levels of CAT (P<0. 01), SOD (P<0. 01) and GR (P<0. 001) enzymes in the mice hippocampus compared to those in the pilocarpine group. Conclusion: The findings of this study indicate that the antioxidant effect of PIOGLITAZONE may play an important role in its protective effects against neuronal damage caused by pilocarpineinduced seizure.

Objective(s): Testicular torsion/detorsion (T/D) is a well-known cause for infertility. PIOGLITAZONE is an agonist of peroxisome proliferator activated receptor-gamma (PPAR-γ ). Previous studies have shown that PIOGLITAZONE has anti-inflammatory, antioxidant and antiapoptotic properties. The present study hypothesized that PIOGLITAZONE may be protective against the testicular T/D tissue insults, and the possible pathophysiological mechanisms involved in this effect were also investigated. Materials and Methods: Rats were randomly divided into four groups: sham group, T/D group where testicular torsion was performed for 4 hr followed by 4 hr of detorsion and two PIOGLITAZONE-treated groups (1 mg/kg and 3 mg/kg, by single intraperitoneal injection 30 min prior to detorsion). At the end of reperfusion period, blood, ipsilateral and contralateral testicular tissue samples were obtained for biochemical and histopathological examination. Results: PIOGLITAZONE reduced oxidative tissue damages, inflammatory mediators, and apoptotic markers and enhanced the total antioxidant status, and AMP-activated protein kinase level. Moreover, PIOGLITAZONE improved spermatogenesis evidenced by increased Johnsen’ s score and reversed the histopathological damages induced by testicular T/D. The effects of PIOGLITAZONE were higher with the dose of 3 mg/kg. Conclusion: PIOGLITAZONE exhibited a protective effect against the deleterious actions of testicular T/D. This beneficial potential of PIOGLITAZONE may be attributed to its antioxidant, anti-inflammatory and antiapoptotic properties, which was more obvious with the dose of 3 mg/kg. PIOGLITAZONE may be a promising therapy for testicular T/D.

BACKGROUND: Increased proteinuria would lead to a larger risk for renal failure in the long term. Therefore, proteinuria requires immediate and thorough evaluation. This study was designed to evaluate the effects of PIOGLITAZONE on proteinuria in patients with non-diabetic renal disease.METHODS: In this self-controlled clinical trial study, forty four non-diabetic patients aged 18 and more, who had renal disease and a stable proteinuria of over 0.5 g in 24 hour, were studied. All patients received 15 mg of daily PIOGLITAZONE for 4 months. Urine protein excretion was measured as a main end point prior to the study, at the end of the 2nd and 4th months of treatment, and 2 and 4 months after the cessation of the active drug. Other evaluated variables included systolic blood pressure, serum creatinine, urea, alanine aminotransferase (ALT), aspartate aminotransferase (AST), fasting blood sugar (FBS), blood urea nitrogen (BUN) and glomerular filtration rate (GFR) levels.RESULTS: Proteinuria (mean ± SEM) prior to the study, at the 2nd and 4th months of the treatment, and 2 and 4 months after the cessation of PIOGLITAZONE were 1088.6±131.1, 699.9±118.3, 433.9±68.7, 416.1±54.9 and 646.9±89.1, respectively (p<0.001). In addition, the reduction of 24-hour urine protein was statistically significant for both male and female patients (p<0.001 for both).CONCLUSIONS: A reduction of proteinuria in patients with non-diabetic renal disease was observed during the 4-month treatment with PIOGLITAZONE which continued for 2 months after the cessation of the treatment. However, 4 months after the cessation of the treatment, a little increase was detected in the level of proteinuria.