Tulsi oil as a potential penetration enhancer for celecoxib transdermal gel formulations.

The focus of the present study was to develop and evaluate the transdermal system of celecoxib. Transdermal gels composed of carbopol 940 in propylene glycol (PG) containing penetration enhancers. The formulations were characterized by permeation, pharmacokinetics, pharmacodynamics and histopathology. Celecoxib permeation across excised rat skins were statistically (p < 0.05) enhanced by tulsi oil compared to turpentine oil containing formulations. In comparison to orally administered formulations, the pharmacokinetic parameters of gel and control formulations were significantly higher (p < 0.05). The maximum plasma concentration (Cmax) obtained with formulations containing 4% turpentine and 6% tulsi oil was, respectively, 1.52 and 2.41 times higher than the formulations without penetration enhancer. Similarly, area under the curve (AUC) of these formulations was 1.70 and 2.40 times higher than the formulations without penetration enhancers. Anti-inflammatory studies demonstrated a statistically significant (p < 0.05) pharmacodynamics profile for the transdermal gel formulations compared to orally administered and control celecoxib formulations. Histopathological studies revealed some disruption in the epidermis without any toxic effect on the dermis layer of skin by penetration enhancers. In summary, the transdermal gel formulations of celecoxib containing penetration enhancers sustained drug level in the blood and will reduce the dose frequency as required with its conventional oral formulation.

Protective effects of aliskiren in doxorubicin-induced acute cardiomyopathy in rats.

In this study, effect of aliskiren (ALK) on doxorubicin (DXR)-induced cardiomyopathy in rats was evaluated. ALK (50 and 100 mg/kg/day) was administered for 7 days and a single intraperitoneal injection of DXR (20 mg/kg) on day 5. The animals were sacrificed 48 h after DXR administration. DXR produced significant elevation in malondialdehyde (MDA) and significantly inhibited the activity of glutathione (GSH) in heart tissue, with a significant rise in the serum levels of lactate dehydrogenase (LDH), total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL) and reduction in high-density lipoprotein (HDL), indicating acute cardiac toxicity. ALK pretreatment significantly reduced the MDA concentration and ameliorated the inhibition of cardiac GSH activity. ALK also significantly improved the serum levels of LDH, TC, TG, LDL and reduction in HDL in DXR-treated rats. Furthermore, histological examination of the heart sections confirmed the myocardial injury with DXR administration and the near-normal pattern with ALK pretreatment. The results provide clear evidence that the ALK pretreatment offered significant protection against DXR-induced enzymatic changes and cardiac tissue damage.

Insights into liaison between antiepileptic drugs and bone.

The adverse effect on bone caused by chronic anticonvulsant therapy causes multiple abnormalities in calcium and bone metabolism, varying from bone turnover, without significant loss of cortical or trabecular bone, to osteopenia/osteoporosis and to osteomalacic disorder. The studies conducted to date have documented anticonvulsant bone disease as a state of increased bone remodeling. With the newer antiepileptic drugs (AEDs) gaining importance and starting to replace conventional medicines, it may be appropriate to compare them with the conventional AEDs and to examine their impact on multiple aspects of bone health. This review focuses on the status of the bony effects of AEDs.

Protective effects of telmisartan against acute doxorubicin-induced cardiotoxicity in rats.

The therapeutic usefulness of doxorubicin (DXR), an anthracycline antibiotic, is limited by its cardiotoxicity. The present study investigated the effects of telmisartan, an angiotensin II receptor (AT1) antagonist against doxorubicin-induced cardiotoxicity in rats using biochemical and histopathological approaches. Doxorubicin (20 mg/kg) was injected intraperitoneally (ip) as a single dose and telmisartan (10 mg/kg) was administered orally for 7 days. Rats treated with DXR showed cardiotoxicity as evidenced by elevation of serum lactate dehydrogenase (LDH) activity, tissue malondialdehyde (MDA) level, catalase activity and a decrease in the level of glutathione (GSH). Pre- and post-treatment with telmisartan elicited a significant decrease in the activities of LDH and catalase in comparison with DXR-treated group. Furthermore, pretreatment with telmisartan also decreased lipid peroxidation (MDA level) and increased the GSH content in comparison with DXR group. However, the difference in lipid peroxidation and GSH content were not statistically significant in post-treated group. Histopathological studies showed disruption of cardiac tisuues in DXR groups. Pre- and post-treatment with telmisartan reduced the damage of cardiac tissue in rats. These results suggest that telmisartan treatment provides a significant protective effect against acute-doxorubicin induced cardiotoxicity in rats.