Sepsis caused by infection is one of the most important problems of clinical medicine. This study aimed to determine the effect of Apilarnil (API), a bee product, on lipopolysaccharide (LPS) induced liver injury. In the study, 64 adult Sprague-Dawley rats were divided into eight groups; control, 0.2, 0.4 and 0.8 g / kg apilarnil (API) treated groups, LPS (30 mg / kg) group, LPS + 0.2, LPS + 0.4 and LPS + 0.8 g / kg API. At tissues obtained from rats, histopathological evaluation, biochemical analysis by ELISA (Catalase-CAT, malondialdehyde-MDA, superoxide dismutase-SOD, xanthine oxidase-XOD, and testican 1-TCN-1), immunohistochemical evaluation (Toll-like receptor 4 (TLR4), High Mobility Group Box Protein 1 (HMGB-1), nuclear factor kappa B (NF-κB), Tumor necrosis factor-alpha (TNF-α), Interleukin 1 beta (IL-1β), Interleukin 6 (IL-6) and Inducible nitric oxide (iNOS)), TUNEL analysis to determine the number of apoptotic cells and Comet test as an indicator of DNA damage were performed. Histopathological examination revealed dilated blood vessels, inflammatory cell infiltration, and pyknotic nuclei damaged hepatocytes in the liver tissues of the LPS group. It was found that tissue damage was decreased significantly in LPS + API treatment groups compared to the LPS group. The number of TUNEL positive cells observed in the LPS group in liver samples increased compared to control and API-treated groups only (p < 0.05). The number of TUNEL positive cells showed a statistically significant decrease compared to the LPS group in the groups treated with LPS + API. LPS treatment increased MDA, XOD, and TCN 1 levels and decreased SOD and CAT levels; this effect was reversed in the groups treated with LPS + API. In the LPS group, DNA damage was significantly increased when compared with the LPS + API. LPS treatment increased expression of TLR4, HMGB-1, NF-κB, iNOS, TNF-α, IL-1β, IL-6; in the groups treated with LPS + API reduced this increase. In conclusion, apilarnil administered in rats may be thought to prevent LPS-induced liver damage by inhibiting the TLR4 / HMGB-1 / NF-κB signaling pathway.

Doxorubicin (DOX) is used for treatment of many cancer types. Thymoquinone (THQ) is a powerful antioxidant agent used for reducing side effects of several drugs. The aim of this study is to determine possible therapeutic effects of THQ on doxorubicin-induced testicular toxicity in rats. Rats were divided into five groups (n = 8): control, THQ, olive oil, DOX (a single dose of 15 mg/kg intraperitoneally (i.p.) on seventh day of the experiment), and DOX + THQ (10 mg/kg THQ per day and 15 mg/kg DOX i.p. on seventh day). Animals were euthanized, and testis tissues were evaluated histopathologically. Caspase 3 and HSP90 immunostaining were performed to determine the expression levels of these proteins among groups. Terminal deoxynucleotidyl transferase 2′-deoxyuridine, 5′-triphosphate nick-end labeling method was used for evaluation of apoptotic index. Moreover, serum testosterone levels and total antioxidant status (TAS) and total oxidant status (TOS) in testicular tissue were measured by ELISA assay. The DOX group had histopathological deterioration compared to the control group. There was an increase in apoptotic index, caspase 3 and HSP90 expressions in the DOX group. While TAS level of the DOX group decreased, TOS level increased when compared with the other groups. Serum testosterone levels in the DOX group decreased compared to the control group. However, there was improvement in testicular tissue in DOX + THQ group compared to the DOX group. There was a decrease in apoptotic index, caspase 3, and HSP90 expressions in DOX + THQ group compared to the DOX group. Testosterone level of DOX + THQ significantly increased compared to the DOX group. We suggest that THQ can be used as a protective agent to reduce the toxic effects of DOX.

Doxorubicin (DOX) is used as an anticancer drug despite its many side effects. Thymoquinone (THQ) is a plant-derived substance that exhibits antioxidant and anti-inflammatory properties. We investigated the protective effects of THQ on DOX induced nephrotoxicity in rats. Rats were divided into five groups of eight: group 1, untreated control; group 2, olive oil group given olive oil intraperitoneally (i.p.) for 14 days; group 3, THQ group given 10 mg/kg THQ i.p. for 14 days; group 4, DOX group given a single dose of 15 mg/kg DOX i.p. on day 7 of experiment; group 5, DOX + THQ given 10 mg/kg THQ i.p. for 14 days and 15 mg/kg DOX i.p. on day 7. Kidney tissues were evaluated for histopathology. Caspase-3, IL-17, GRP78 and TNF-α immunostaining was used to determine the expression levels of these proteins among the groups. The TUNEL method was used to determine the apoptotic index. Total antioxidant status (TAS), total oxidant status (TOS), and TNF-α and TGF-β1 levels in kidney tissue were measured using ELISA assay. Histopathologic damage, caspase-3, IL-17, GRP78 and TNF-α immunoreactivity, TUNEL positive cells, TOS, TNF-α and TGF-β1 levels were increased in group 4 compared to group 1. The TAS of group 4 decreased compared to group 1. We found decreased caspase-3, IL-17, GRP78 and TNF-α expressions and TUNEL positive cells in group 5 compared to group 4. In rats given DOX, THQ reduced kidney damage by suppressing endoplasmic reticulum stress, inflammation and apoptosis pathways.