Evaluation of a multifunctional staphylokinase variant with thrombin inhibition and antiplatelet aggregation activities produced from salt-inducible E. coli GJ1158.

Reocclusion is one of the major root causes for secondary complications that arise during thrombolytic therapy. A multifunctional staphylokinase variant SRH (staphylokinase (SAK) linked with tripeptide RGD and didecapeptide Hirulog) with antiplatelet and antithrombin activities in addition to clot specific thrombolytic function, was developed to address the reocclusion problem. We preferred to use Escherichia coli GJ1158 as the host in this study for economic production of SRH by osmotic (0.3 mol/L sodium chloride) induction, to overcome the problems associated with the yeast expression system. The therapeutic potential of SRH was evaluated in the murine model of vascular thrombosis. The SAK protein (1 mg/kg body mass) and SRH protein (1 mg/kg and 2 mg/kg) were administered intravenously to the different treatment groups. The results have shown a dose-dependent antithrombotic effect in carrageenan-induced mouse tail thrombosis. The thrombin time, activated partial thromboplastin time, and prothrombin time were significantly prolonged (p < 0.05) in the SRH-infused groups. Moreover, SRH inhibited platelet aggregation in a dose-dependent manner (p < 0.05), while the bleeding time was significantly (p < 0.05) prolonged. All of these results inferred that the osmotically produced multifunctional fusion protein SRH (SAK-RGD-Hirulog) is a promising thrombolytic agent, and one which sustained its multifunctionality in the animal models.

Influence of losartan on the hypoglycemic activity of glimepiride in normal and diabetic rats.

BACKGROUND: The influence of losartan on the hypoglycemic effect of glimepiride was studied in normal and diabetic rats. METHOD: Losartan and glimepiride were studied at a dose of 4.5 and 0.09 mg/kg and in normal and diabetic rats, respectively. The blood samples were collected at 0, 1, 2, 3, 4, 6, 8, 10, 12, and 16 hours and analyzed for glucose levels using a glucometer. RESULTS: Glimepiride exhibited a maximum reduction of blood glucose levels at the 4th hour in normal and diabetic rats. The maximum hypoglycemic effect was observed at the 6th hour in normal rats treated with losartan. In normal rats, losartan did not have any significant effect on the hypoglycemic activity of glimepiride in either the single- or multiple-dose interaction study. In the case of diabetic rats, losartan did not have any significant effect on the hypoglycemic activity of glimepiride in the single-dose interaction study, but a significant change was observed in the multiple-dose study of diabetic rats. Hence, the interaction was found to be pharmacodynamic. CONCLUSIONS: The study indicates that chronic losartan pretreatment elevates the hypoglycemic effect of glimepiride by a possible rise in insulin sensitivity and improving insulin homeostasis or may be due to the inhibition of CYP2C9. The study also suggests that caution may be recommended concerning combined use of losartan and an oral hypoglycemic agent, glimepiride.

Protective effect of Livactine against CCl(4) and paracetamol induced hepatotoxicity in adult Wistar rats.

BACKGROUND: Liver disease has become one of the serious health problems as it is exposed to many kinds of xenobiotics and therapeutic agents. Moreover the rapidly growing morbidity and mortality from liver disease are attributable to the increasing number of chemical compounds and environmental pollution. Unfortunately, so far, in the modern era of medicine there is no specific treatment to counter the menacing impact of these dreaded diseases. Many polyherbal formulations are used widely to treat these disorders. Livactine is a polyherbal formulation and is claimed to be useful in jaundice and biliary dysfunctions. Most of these formulations do not have standard and approved reports stating their pharmacological action or therapeutic efficacy. Therefore, there is a need for experimental confirmation of the pharmacological effects of this formulation. The rationale behind the selection of carbon tetrachloride is due to its free radical mechanism based liver injury, and paracetamol is consumed widely by the human population and it is also a potential liver hazard. AIM: To evaluate the anti-hepatotoxic activity of Livactine against carbon tetrachloride & paracetamol induced toxicity in rats. MATERIAL AND METHODS: Albino rats of Wistar strain were used to evaluate the hepatoprotective activity of Livactine against carbon tetrachloride & paracetamol induced toxicity. Liver damage was assessed by estimating various biochemical parameters such as serum glutamate oxaloacetate transaminase, serum glutamate pyruvate transaminase, lactate dehydrogenase, alkaline phosphatase, acid phosphatase, total bilirubin, and total protein. The results of the rats treated with Livactine were compared with that of Liv-52. RESULTS: Livactine showed significant dose dependent hepatoprotective effect by reducing elevated serum enzyme levels when compared to that of Liv-52. CONCLUSION: Our findings confirm that the formulation was found to be effective pharmacologically at higher dose against carbon tetrachloride and paracetamol induced hepatotoxic models and were comparable to that of Liv-52. The resultant hepatoprotective activity of Livactine could be due to its free radical scavenging property of the ingredients.