A 28-days sub-acute toxicity study in swiss albino mice to evaluate toxicity profile of neurotol plus (mannitol and glycerol combination).

Osmotic agents are still the most common treatment options available for controlling intracranial pressure (ICP). Combining Mannitol and Glycerol provides a better alternative and is currently available as best therapy used for increased ICP. The aim of this work was to study the effects of repeated dosing (28 days) of Mannitol 20% and Glycerol 10% combined formulation, Neurotol plus on safety profile. A twenty eight days sub-acute toxicity study was conducted at three different dose levels of 5ml/kg, 10 ml/kg and 20 ml/kg. Mice were randomly divided into four groups of six animals each. Physical parameters, biochemical parameters related to liver toxicity & nephrotoxicity and hematological parameters were studied as end point of evaluation. We also carried out histopathlogical studies to assess any organ specific toxicity. The present study demonstrated that there were either no or very minimal changes (at high dose) were observed on various physical, biochemical and hematological parameters between Neurotol plus and control group. In conclusion the data of present study suggest that the combination of Mannitol and Glycerol is not associated with any serious adverse effects and is safe therapeutic choice for ICP reduction.

Tannic acid prevents azidothymidine (AZT) induced hepatotoxicity and genotoxicity along with change in expression of PARG and histone H3 acetylation.

Azidothymidine (AZT) is known to decrease HIV virus replication and is one of the most frequently prescribed antiretroviral drugs used for AIDS treatment. Dose-limiting toxicities are the major curse associated with AZT therapy. Recently, we have reported that tannic acid; a PARG inhibitor prevents cisplatin induced nephrotoxicity. The present work was conceived to study the effect of tannic acid on AZT induced hepatotoxicity and genotoxicity. AZT induces increase in plasma levels of ALT, AST and alkaline phosphatase along with increase in micronucleus (MN) count in peripheral blood. Suggesting, AZT is hepatotoxic and genotoxic to mice. Treatment of tannic acid protects AZT induced hepatotoxicity by decreasing the ALT, AST and alkaline phosphatase levels. It also significantly reduces the oxidative damage by preventing reduction in glutathione and decreasing the level of malondialdehyde in liver of AZT treated mice. In addition, tannic acid decreases the PARG expression, PARP cleavage and histone H3 acetylation in liver of AZT treated mice. Moreover, treatment of tannic acid also decreases MN count in peripheral blood, suggesting its anti-mutagenic effect. In light of these findings we suggest the potential role of tannic acid treatment in preventing AZT induced toxicity.