Safety Assessment of Ubiquinol Acetate: Subchronic Toxicity and Genotoxicity Studies.

Coenzyme Q10 (CoQ10) is a lipid soluble, endogenous antioxidant present at highest levels in the heart followed by the kidney and liver. The reduced CoQ10 ubiquinol is well known for its chemical instability and low bioavailability. The present study was designed to synthesize ubiquinol acetate, which is more stable and biologically active, and further evaluate its safety and genotoxic potential. Synthesized ubiquinol acetate showed better stability than that of ubiquinol at the end of 3 months. In vitro genotoxicity studies (AMES test, in vitro micronucleus and chromosomal aberration) showed ubiquinol acetate as nongenotoxic with no clastogenic or aneugenic effects at high dose of 5000 and 62.5 µg/mL, respectively. In subchronic toxicity study, ubiquinol acetate was administered orally to Sprague Dawley rats at 150, 300, and 600 mg/kg/day for 90 days. No treatment related adverse effects were observed in males at 600 mg/kg/day; however, females showed treatment related increase in AST and ALT with small focal irregular white-yellow spots in liver on gross necropsy examination. Histopathological evaluation revealed hepatocellular necrosis in high dose females which was considered as adverse. Based on the results, the No-Observed-Adverse-Effect Level (NOAEL) of ubiquinol acetate in males and females was determined as 600 and 300 mg/kg/day, respectively.

Scientific validation of the different purification steps involved in the preparation of an Indian Ayurvedic medicine, Lauha bhasma.

ETHNOPHARMACOLOGICAL RELEVANCE: Lauha bhasma (iron ash) is one of the iron-based herbo-metallic preparations used in Ayurvedic medicine for treating various ailments due to iron deficiency. MATERIALS AND METHODS: The preparation of Lauha bhasma (iron ash) requires normal purification (heat treatment in vegetable and animal products), special purification (treatment with herbal constituents) and calcination steps aimed at converting the raw material to a suitable therapeutic form. In this study, we have systematically and scientifically evaluated through a series of qualitative tests and modern analytical tools the importance of the treating media. RESULTS: Our data demonstrates that these steps are necessary to remove the grease and scales in the raw material. While heating, microcracks appeared on the surface of the iron, which improved the reactivity with the herbal constituents in addition to incorporating nanostructured features. Further, the use of plant products facilitated the removal of Fe³âº present in the raw material by forming soluble complexes. The Fe²âº present in the raw materials also forms an insoluble complex with the herbal constituents in the presence of UV radiation. CONCLUSIONS: In conclusion, our data summarily suggest that the purification steps involved in the preparation of Lauha bhasma (iron ash) are critical.

Mercury-based traditional herbo-metallic preparations: a toxicological perspective.

This review aims to explore the toxicological aspects of mercury-based herbo-metallic preparations like cinnabar and "Rasasindura" that are primarily composed of mercuric sulfide (HgS). Cinnabar-containing preparations have been used extensively in Indian and Chinese systems of medicine for treatment of chronic ailments like syphilis, high fever, pneumonia, insomnia, nervous disorders, deafness, and paralysis of the tongue. Contrary to Western medicine, which does not promote the use of mercury due to its toxic effects, Indian and Chinese traditional practitioners believe that mercury-based formulations have potent therapeutic efficacy, while there is no toxicity due to the unique and repeated purification processes employed during preparation. However, lack of proper pharmacovigilance and widespread self-medication has resulted in undesirable effects to certain sections of the consumers of these preparations, which have contributed to the negative publicity for these forms of medicine. Variations in the quality of the preparations coupled with the lack of understanding of the differences in the recommended dosages and treatment strategies adopted by traditional medicine practitioners, further fuels concerns in the Western world on the safety and efficacy of traditional medicine. But in spite of these concerns, concerted efforts to understand the biological interactions and transformations of these preparations are yet to gain momentum. Although scattered reports on the toxicity of these preparations are available in literature, their mechanism of action has not been conclusively established. Long-term pharmacotherapeutic and in-depth toxicity studies are needed to address the apprehensions raised by these herbo-metallic preparations. This review highlights the lacunae in the studies conducted thus far, and assesses the need for further studies to provide significant data to establish the safety and efficacy of such preparations, as well as develop gold standards for stringent quality control of these preparations.