Background and aims Chronic exposure to chemotherapeutics can lead to severe adverse events including hepatotoxicity. A combination chemotherapy regimen of doxorubicin (DOX) and cyclophosphamide (CPS) is employed in treatment of several cancers such as leukemia, lymphoma, and breast cancer. It is not well understood whether a combination therapy with DOX and CPS can induce hepatotoxicity. We therefore sought to determine whether co-administration of DOX and CPS at their clinically relevant doses and frequency results in hepatotoxicity. Methods Male C57BL/6J mice received one intraperitoneal injection of saline or DOX-2 mg/kg and CPS-50 mg/kg once a week for 4 weeks. After the treatment period, liver histology and various serum biomarkers of hepatotoxicity were assessed. Results Co-treatment with DOX and CPS did not alter the serum levels of alanine aminotransferase (ALT), alkaline phosphatase (ALP), bilirubin, albumin, globulin, or total protein. Similarly, co-administration of DOX and CPS did not result in a noticeable change in liver histology. However, it was notable that the concomitant treatment with DOX and CPS resulted in a significant increase in serum levels of aspartate aminotransferase (AST). Elevated serum AST levels were also associated with increased serum creatinine kinase (CK) levels, suggesting that the elevated serum AST levels are likely due to muscle injury following the co-administration of DOX and CPS. Conclusions Taken together, our results, for the first time, suggest that co-administration of DOX and CPS, at their clinically relevant doses and frequency does not induce a significant hepatotoxicity in the mice.

BACKGROUND: The aim of the study was to compare serum sclerostin levels in human im-munodeficiency virus (HIV)-infected patients and healthy controls, and to evaluate their relationship with bone turnover markers (BTM) and bone mineral density (BMD). METHODS: We prospectively studied 33 HIV treatment-naive patients and 63 healthy individuals; matched for age and sex. Serum sclerostin levels, BTM, BMD were measured. Viral load and cluster of differentiation 4 (CD4) levels were also assessed in HIV-infected patients. RESULTS: The mean+/-standard deviation (SD) age of sample was 37.6+/-10.3 years (range, 19 to 59 years). Of the 96 subjects, 58 (60.4%) were male and 38 (39.6%) were female. Infection with HIV is associated with significant reduction in serum sclerostin levels (HIV-infected: 39.4+/-28.3 vs. non HIV: 76.6+/-15.7 pmol/L; P<0.001) and a decrease in BMD at femoral neck and lumbar spine compared to healthy controls. Sclerostin however was not correlated with BMD and was not related to age, generally a strong correlation. There were no significant correlations between sclerostin and BTM (P>0.05). CONCLUSIONS: These findings suggest that untreated HIV and the resulting immune deficiency and/or systemic inflammation could be an important regulator of serum sclerostin in this population.
Bone Density ; Densitometry* ; Female ; Femur Neck ; Glycoproteins ; HIV* ; Humans ; Humans* ; Inflammation ; Male ; Osteoporosis ; Prospective Studies ; Saudi Arabia ; Spine ; Viral Load