In vivo toxicological evaluation of barium-doped bioactive glass in rats.

Bioactive glasses (BGs) are inorganic biomaterials with several FDA-approved marketed products, mainly for orthopedic and dental applications. However, in the last few decades, the soft tissue regenerative potential of BGs has also been established preclinically, and its clinical translation requires elaborate in vivo toxicity studies for future biomedical applications. Thus, in the present study, we evaluated the comparative acute and sub-acute toxicity of orally administered barium-doped BG (BaBG) with 45S5 in rats. The lethal dose (LD 50) of BaBG and 45S5 was more than 2000 mg/kg body weight (b.w.), with no mortality at the highest dose tested. The oral acute toxicity study was performed at doses of 300 and 2000 mg/kg b.w. according to OECD 423. The organ coefficients of vital organs and histological analysis affirmed the safety profile of BaBG. Moreover, various biochemical indices like alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), creatinine, and CK-MB confirmed that BaBG did not cause organ toxicity at all doses tested. Similarly, the repeated dose 28-days sub-acute toxicity study was performed according to OECD 407 at doses 50, 500, and 1000 mg/kg b.w. There was no alteration in the hematological parameters, which ascertains that BaBG had no toxic effects on the hematopoietic centers like 45S5. Furthermore, there was no observed neuro-behavioral toxicity of 45S5 and BaBG. Thus, these findings confirm that BaBG is non-toxic and can be used for therapeutic applications in different disease models. [Display omitted] • The LD 50 of BGs (BaBG and 45S5) is more than 2000 mg/kg b.w. as per OECD 423. • Single oral dosage of BaBG did not alter AST, ALT, Ca2+, Ck-MB level like 45S5. • There was no observed neuro-behavioral toxicity during sub-acute toxicity study. • Hematological parameters were not affected after 28 days oral administration of BaBG. • Histological analysis revealed no sign of organ toxicity in male and female rats. [ABSTRACT FROM AUTHOR]