Caffeine mitigates tamoxifen-induced fatty liver in Wistar rats.

PURPOSE: Tamoxifen, a widely used drug for breast cancer treatment, is associated with adverse effects on the liver, including the development of fatty liver. This study aimed to investigate the potential protective effect of caffeine against tamoxifen-induced fatty liver in Wistar rats. METHODS: Rats were divided into normal control, tamoxifen + saline, and tamoxifen + caffeine. Plasma samples were assessed for biochemical markers related to oxidative stress, inflammation, liver function, and cell damage. Additionally, liver histopathology was examined to quantify the extent of fatty infiltration. RESULTS: In the tamoxifen + saline group, elevated levels of plasma malondialdehyde (MDA), tumor necrosis factor-alpha (TNF-α), alanine aminotransferase (ALT), cytokeratin 18, and soluble ST2 were observed compared to the normal control group, indicating increased oxidative stress, inflammation, and liver injury (p < 0.01). Moreover, histopathological examination revealed a significant increase in fatty infiltration (p < 0.001). However, in the tamoxifen + caffeine group, these markers were markedly reduced (p < 0.05, p < 0.01), and fatty infiltration was significantly mitigated (p < 0.001). CONCLUSIONS: The findings suggest that caffeine administration attenuates tamoxifen-induced fatty liver in rats by ameliorating oxidative stress, inflammation, liver injury, and cell damage. Histopathological evidence further supports the protective role of caffeine. This study highlights the potential of caffeine as a therapeutic intervention to counter tamoxifen-induced hepatic complications, contributing to the optimization of breast cancer treatment strategies.

Caffeine mitigates tamoxifen-induced fatty liver in Wistar rats

Purpose: Tamoxifen, a widely used drug for breast cancer treatment, is associated with adverse effects on the liver, including the development of fatty liver. This study aimed to investigate the potential protective effect of caffeine against tamoxifen-induced fatty liver in Wistar rats. Methods: Rats were divided into normal control, tamoxifen + saline, and tamoxifen + caffeine. Plasma samples were assessed for biochemical markers related to oxidative stress, inflammation, liver function, and cell damage. Additionally, liver histopathology was examined to quantify the extent of fatty infiltration. Results: In the tamoxifen + saline group, elevated levels of plasma malondialdehyde (MDA), tumor necrosis factor-alpha (TNF-α), alanine aminotransferase (ALT), cytokeratin 18, and soluble ST2 were observed compared to the normal control group, indicating increased oxidative stress, inflammation, and liver injury (p < 0.01). Moreover, histopathological examination revealed a significant increase in fatty infiltration (p < 0.001). However, in the tamoxifen + caffeine group, these markers were markedly reduced (p < 0.05, p < 0.01), and fatty infiltration was significantly mitigated (p < 0.001). Conclusions: The findings suggest that caffeine administration attenuates tamoxifen-induced fatty liver in rats by ameliorating oxidative stress, inflammation, liver injury, and cell damage. Histopathological evidence further supports the protective role of caffeine. This study highlights the potential of caffeine as a therapeutic intervention to counter tamoxifen-induced hepatic complications, contributing to the optimization of breast cancer treatment strategies.

Autophagy and anti-inflammation ameliorate diabetic neuropathy with Rilmenidine.

PURPOSE: To evaluate the neuroprotective effects of Rilmenidine on diabetic peripheral neuropathy (DPN) in a rat model of diabetes induced by streptozotocin (STZ). METHODS: STZ (60 mg/kg) was administered to adult Sprague-Dawley rats to induce diabetes. On the 30th day after STZ administration, electromyography (EMG) and motor function tests confirmed the presence of DPN. Group 1: Control (n = 10), Group 2: DM + 0.1 mg/kg Rilmenidine (n = 10), and Group 3: DM + 0.2 mg/kg Rilmenidine (n = 10) were administered via oral lavage for four weeks. EMG, motor function test, biochemical analysis, and histological and immunohistochemical analysis of sciatic nerves were then performed. RESULTS: The administration of Rilmenidine to diabetic rats substantially reduced sciatic nerve inflammation and fibrosis and prevented electrophysiological alterations. Immunohistochemistry of sciatic nerves from saline-treated rats revealed increased perineural thickness, HMGB-1, tumor necrosis factor-α, and a decrease in nerve growth factor (NGF), LC-3. In contrast, Rilmendine significantly inhibited inflammation markers and prevented the reduction in NGF expression. In addition, Rilmenidine significantly decreased malondialdehyde and increased diabetic rats' total antioxidative capacity. CONCLUSIONS: The findings of this study suggest that Rilmenidine may have therapeutic effects on DNP by modulating antioxidant and autophagic pathways.

Autophagy and anti-inflammation ameliorate diabetic neuropathy with Rilmenidine

Purpose: To evaluate the neuroprotective effects of Rilmenidine on diabetic peripheral neuropathy (DPN) in a rat model of diabetes induced by streptozotocin (STZ). Methods: STZ (60 mg/kg) was administered to adult Sprague-Dawley rats to induce diabetes. On the 30th day after STZ administration, electromyography (EMG) and motor function tests confirmed the presence of DPN. Group 1: Control (n = 10), Group 2: DM + 0.1 mg/kg Rilmenidine (n = 10), and Group 3: DM + 0.2 mg/kg Rilmenidine (n = 10) were administered via oral lavage for four weeks. EMG, motor function test, biochemical analysis, and histological and immunohistochemical analysis of sciatic nerves were then performed. Results: The administration of Rilmenidine to diabetic rats substantially reduced sciatic nerve inflammation and fibrosis and prevented electrophysiological alterations. Immunohistochemistry of sciatic nerves from saline-treated rats revealed increased perineural thickness, HMGB-1, tumor necrosis factor-α, and a decrease in nerve growth factor (NGF), LC-3. In contrast, Rilmendine significantly inhibited inflammation markers and prevented the reduction in NGF expression. In addition, Rilmenidine significantly decreased malondialdehyde and increased diabetic rats' total antioxidative capacity. Conclusions: The findings of this study suggest that Rilmenidine may have therapeutic effects on DNP by modulating antioxidant and autophagic pathways.

Antifibrotic preventive effect of polyethylene glycol (PEG) 3350 in methotrexateinduced hepatoxicity model.

PURPOSE: Liver damage caused by drugs and other chemicals accounts for about 5% of all cases. Methotrexate (MTX), a folic acid analogue, is a first-line synthetic antimetabolite agent routinely used in the treatment of rheumatoid arthritis and other autoimmune and chronic inflammatory diseases. Polyethylene glycol (PEG) has antioxidant activity. In this study, we evaluated biochemically and histopathologically the antifibrotic effect of PEG 3350 administered intraperitoneally to prevent methotrexate-induced liver damage in rats. METHODS: A total of 30 male rats including 10 rats was given no drugs (normal group), and 20 rats received single-dose 20 mg/kg MTXfor induced liver injury in this study. MTX was given to 20 rats, which were divided in two groups. Group 1 rats was given PEG30 mg/kg/day (Merck) intraperitoneally, and Group 2 rats % 0.9 NaCl saline 1 mL/kg/day intraperitoneally daily for two weeks. RESULTS: Transforming growth factor beta (TGF-ß), plasma malondialdehyde (MDA), liver MDA, serum tumour necrosis factor alpha (TNF-α), alanine aminotransferase and plasma pentraxin-3 levels and, according to tissue histopathology, hepatocyte necrosis, fibrosis and cellular infiltration were significantly better in MTX+PEG group than in MTX+saline group. CONCLUSIONS: PEG 3350 is a hope for toxic hepatitis due to other causes, since liver damage occurs through oxidative stress and cell damage, similar to all toxic drugs.

Antifibrotic preventive effect of polyethylene glycol (PEG) 3350 in methotrexateinduced hepatoxicity model

Purpose: Liver damage caused by drugs and other chemicals accounts for about 5% of all cases. Methotrexate (MTX), a folic acid analogue, is a first-line synthetic antimetabolite agent routinely used in the treatment of rheumatoid arthritis and other autoimmune and chronic inflammatory diseases. Polyethylene glycol (PEG) has antioxidant activity. In this study, we evaluated biochemically and histopathologically the antifibrotic effect of PEG 3350 administered intraperitoneally to prevent methotrexate-induced liver damage in rats. Methods: A total of 30 male rats including 10 rats was given no drugs (normal group), and 20 rats received single-dose 20 mg/kg MTXfor induced liver injury in this study. MTX was given to 20 rats, which were divided in two groups. Group 1 rats was given PEG30 mg/kg/day (Merck) intraperitoneally, and Group 2 rats % 0.9 NaCl saline 1 mL/kg/day intraperitoneally daily for two weeks. Results: Transforming growth factor beta (TGF-ß), plasma malondialdehyde (MDA), liver MDA, serum tumour necrosis factor alpha (TNF-α), alanine aminotransferase and plasma pentraxin-3 levels and, according to tissue histopathology, hepatocyte necrosis, fibrosis and cellular infiltration were significantly better in MTX+PEG group than in MTX+saline group. Conclusions: PEG 3350 is a hope for toxic hepatitis due to other causes, since liver damage occurs through oxidative stress and cell damage, similar to all toxic drugs.