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Background: Age-related differences in the ethoxyresorufin O-deethylase (EROD) activity of CYP1A1 and its inducibility in rats may determine the toxic potential of acetaminophen.  This study was carried out to compare the effects of acetaminophen (APAP) and β-naphthoflavone (βNF) on CYP1A1 activity in young and adult rats. Methods: For this purpose, young and adult rats (n = four / group) were treated with different doses of APAP. Likewise groups of young and adult rats were treated with a single dose of β-naphthoflavone (βNF, 67 mg / kg b.w). EROD was measured in microsomal fraction using resorufin as the substrate. Results:The results showed that a single i. p. injection of APAP (25 mg / kg B.W.) failed to alter liver microsomal EROD in young and adults. Whereas, in adults treated with 250 and 450 mg APAP / kg B.W, liver CYP1A1 was elevated to about 45 and 60% respectively. The rate of CYP1A1 induction in young rats with single dose of APAP (450 mg/kg B.W) was approximately 32%. Induction in CYP1A1 was noticed 4 h after APAP injection and returned to normal levels in 24 h. The inducibility of CYP1A1 in rats treated with a toxic dose of APAP was comparable to the data obtained from animals treated βNF, 67 mg / kg b.w. Conclusion: These results together with our previous reports indicate a similar pattern of changes in CYP1A1 in both the age-groups treated with toxic doses of APAP may suggest that the inducible CYP1A1 can equally contribute to protection against liver damage in young and adult rats.

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Objective: Acetaminophen (APAP) overdose causes acute liver injuries. Studies show that stem cell factor (SCF) and its receptor, c-Kit, enhance liver recovery from APAP-induced injuries in mice. In this study we explore the effect of SCF on activity of glutathione S-transferase (GSTs) enzymes which are considered to be important in APAP metabolism. Methods: We divided 45 Balb/c mice into three groups. Within each group there were three sub-groups of five mice per subgroup. The groups included: 1. APAP (300 mg/kg B.W., i.p.); 2. SCF (40 µg/kg B.W., i.p.) given.30 minutes after APAP (300 mg/kg B.W., i.p.), and 3.control mice treated with normal saline. The mice were sacrificed at 1, 12 and 24 hours, respectively. Hepatotoxicity was evaluated in the 24 hour group by histopathology and assessment of biochemical serum markers (ALT and AST). We assessed the levels of SCF receptor (c-Kit) protein and GST enzyme activities in the liver tissues.  Results: Hepatotoxicity was induced by APAP (300 mg/kg, B.W) as evident by both histopathological observations and a significant (p<0.05) increase in serum ALT and AST levels, which were reversed by SCF administered post-APAP. SCF administration after APAP administration significantly increased GSTs enzyme activity levels by 24 hours, however it led to a significant decrease in c-Kit protein level compared to the control and APAP groups. Conclusion: Our data suggest that SCF binding to its receptor (c-Kit) on liver cells may attenuate APAP-induced liver injuries by increasing GST activities in the livers of mice.

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Objective: There are numerous strategies to prevent hepatotoxicity caused by doxorubicin therapy. These strategies include exercise as well as herbal antioxidants such as curcumin to reduce the toxic effects of doxorubicin. This study aims to evaluate the effects of six weeks of continuous training with and without nanocurcumin supplementation on doxorubicin-induced hepatotoxicity in an aging rat model.
Methods: We randomly divided 42 Wistar male rats into 7 groups: control saline, control doxorubicin, nanocurcumin + doxorubicin, nanocurcumin + saline, continuous training + doxorubicin, continuous training + saline, and continuous training + nanocurcumin + doxorubicin. The rats received intraperitoneal injections of D-galactose (100 mg/kg) to induce ageing. The training groups ran on a treadmill for six weeks, five days per week with a gradual increase from 25 min/day to 54 min/day at a velocity of 15 m/min to 20 m/min. In the last fifteenth days, rats scheduled to received doxorubicin had a cumulative dose of 15 mg/kg of body weight (daily: 1 ml/kg). Nanocurcumin supplement (daily: 100 mg/kg body weight) was administered to the respective groups. Assessment and analysis were conducted after homogenization of the liver tissue biopsy.
Results: Doxorubicin caused a significant decrease in glutathione peroxidase and a slight increase in malondialdehyde in the liver. On the other hand, continuous training with doxorubicin treatment prevented the decrease of glutathione peroxidase and increase in malondialdehyde in the liver that was caused by doxorubicin. Also, six weeks of continuous training with nanocurcumin supplementation caused a significant decrease in malondialdehyde and increased glutathione peroxidase in the liver compared to the control doxorubicin group.
Conclusion: Based on the results, the combination of nanocurcumin supplementation and continuous training in the doxorubicin-induced aging rat model have led to a precautionary effect and up-regulation of antioxidant defense. Continuous training appeared to have more beneficial effects than nanocurcumin supplementation in reducing doxorubicin-induced hepatotoxicity.