Myricetin (3,3',4',5,5',7-hexahydroxyflavone) prevents ethanol-induced biochemical and inflammatory damage in the liver of Wistar rats.

Purpose: The current investigation was carried out to evaluate the efficacy of myricetin in ethanol-induced liver toxicity in Wistar rats. Research Design: Twenty-four rats were randomly divided into four groups with six animals per group. Group-I animals were administered with vehicle (distilled water), Group II, III, and IV were treated orally with sequential (per week) increase in the dose of ethanol (5, 8, 10, and 12 g/kg b wt per week in each group) for 28 days. Myricetin was treated orally to Group-III and IV animals at the respective doses of 25 mg/kg b wt. and 50 mg/kg b wt. Results: Our results showed that myricetin prevented hepatotoxicity by modulating the production of free radicals, ethanol metabolizing enzymes, and inflammatory markers in vivo. Myricetin also helped maintain lipid membrane integrity, oxidant-antioxidant status, and histoarchitecture. Ethanol administration caused elevation in XO, ADH, and CYP2E1 in hepatic tissue, which significantly normalized with myricetin administration. After ethanol administration, there was a steep increase in the hepatotoxicity biomarkers, including ALT, MDA, and AST. The level of cytotoxicity marker LDH also increased after ethanol administration; myricetin administration decreased the level of all these markers. Moreover, myricetin treatment also reduced ethanol-induced inflammatory markers such as NF-κB and IL-6. Conclusion: Findings from the current study demonstrate that myricetin administration prevents alcohol-induced hepatic injury by influencing the metabolism of ethanol, inhibiting oxidative stress, maintaining lipid profile, and suppressing inflammatory markers.

Dose dependent safety implications and acute intravenous toxicity of aminocellulose-grafted-polycaprolactone coated gelatin nanoparticles in mice.

Polymeric nanoparticles (NPs) are the most widely researched nanoformulations and gained broad acceptance in nanotherapeutics for targeted drug delivery and theranostics. However, lack of regulations, guidelines, harmonized standards, and limitations with their employability in clinical circumstances necessitates an in-depth understanding of their toxicology. Here, we examined the in-vivo toxicity of core-shell polymeric NPs made up of gelatin core coated with an outer layer of aminocellulose-grafted polycaprolactone (PCL-AC) synthesized for drug delivery purposes in inflammatory disorders. Nanoparticles were administered intravenously in Swiss albino mice, in multiple dosing (10, 25, and 50 mg/kg body weight) and outcomes of serum biochemistry analysis and histopathology evaluation exhibited that the highest 50 mg/kg administration of NPs altered biochemistry and histopathology aspects of vital organs, while doses of 10 and 25 mg/kg were safe and biocompatible. Further, mast cell (toluidine blue) staining confirmed that administration of the highest dose enhanced mast cell infiltration in tissues of vital organs, while lower doses did not exhibit any of these alterations. Therefore, the results of the present study establish that the NPs disposal in-vivo culminates into alterations in organ structure and function consequences such that lower doses are quite biocompatible and do not demonstrate any structural or functional toxicity while some toxicological effects start appearing at the highest dose.

Evaluation of the hepatotoxic potential of Tinospora crispa and its isolated borapetosides B, C and F in a murine model.

The hepatotoxic potential of the methanolic extract of the stems of Tinospora crispa and of its furano-diterpenoid-borapetosides B, C, and F-was investigated in normal and health-compromised mice. Health-compromised condition was established by a single intraperitoneal injection of LPS (6 mg/kg). Two different sets of experiments were conducted to evaluate the hepatotoxic potential. A 21-day study where the mice were dosed with the extract of T. crispa (1 gm/kg b. wt./day) or standardized combination of borapetosides B, C and F (500 mg/kg b. wt.) with or without a single dose of LPS (1 gm/kg b. wt./day). In the acute toxicity study, mice were dosed with borapetosides B, C, and F (500 mg/kg b. wt.). Results showed that the ALT levels were normal and liver histopathology unaltered. No conclusive hepatotoxicity was observed in the methanolic extract or pure compounds tested under the given experimental conditions.