Therapeutic Potential of Silymarin in Mitigating Paclitaxel-Induced Hepatotoxicity and Nephrotoxicity: Insights into Oxidative Stress, Inflammation, and Apoptosis in Rats.

Background: Paclitaxel (PAX) is a widely used chemotherapy drug for various cancer types but often induces significant toxicity in multiple organ systems. Silymarin (SIL), a natural flavonoid, has shown therapeutic potential due to its multiple benefits. Aims: To evaluate the therapeutic efficacy of SIL in mitigating liver and kidney damage induced by PAX in rats, focusing on oxidative stress, inflammation, and apoptosis pathways. Study Design: Experimental animal model. Methods: The study included 28 male Wistar rats aged 12-14 weeks weighing 270-300 g. The rats were divided into four groups: control, SIL, PAX, and PAX + SIL, with seven in each group. The rats received intraperitoneal (i.p.) injections at a dose of 2 mg per kilogram of body weight of PAX for 5 successive days, followed by oral gavage with 200 mg/kg body mass of SIL for 10 uninterrupted days. We examined the effect of SIL on specific serum biochemical parameters using an autoanalyzer and rat-specific kits. The spectrophotometric methods was used to investigate oxidative stress indicators in kidney and liver tissues. Aquaporin-2 (AQP-2), B-cell lymphoma-2 (Bcl-2), cysteine aspartate-specific protease-3 (caspase-3), interleukin-6 (IL-6), nuclear factor kappa B (NF-κB), and streptavidin-biotin staining were used to assess immunoreactivity in PAX-induced liver and kidney injury models. Results: SIL treatment significantly reduced serum levels of alanine aminotransferase, aspartate aminotransferase, creatinine, urea, and C-reactive protein, indicating its effectiveness in treating PAX-induced liver and kidney injury. SIL treatment significantly reduced oxidative stress by increasing essential antioxidant parameters, such as superoxide dismutase, catalase, glutathione peroxidase, and glutathione. It also reduced malondialdehyde levels in liver and kidney tissues of SIL-PAX groups (p < 0.05). SIL administration reduced NF-κB, caspase-3, and IL-6 expression while increasing Bcl-2 and AQP2 levels in liver and kidney tissues of rats treated with SIL and PAX (p < 0.05). Conclusion: Our findings indicate the potential of SIL to alleviate PAX-induced liver and kidney damage in rats by reducing oxidative stress, inflammation, and apoptotic processes.

Evaluation of the toxicological effects of favipiravir (T-705) on liver and kidney in rats: biochemical and histopathological approach.

Favipiravir is a selective RNA polymerase inhibitor and a broad-spectrum antiviral drug, an important agent used in viral infections, including Ebola, Lassa, and COVID-19. This study aims to evaluate the potential toxicological effects of favipiravir administration on rats' liver and kidney tissues. Favipiravir was applied for five and ten days in the present study. During this period, it was aimed to determine possible toxic effects on the liver and kidney. For this purpose, the impact of favipiravir on liver and kidney tissues were examined using histopathologic and biochemical methods. The present study showed that favipiravir administration led to an elevation in the liver and kidney serum enzymes and oxidative and histopathologic damages. Favipiravir administration caused apoptotic cell death (Caspase-3 and Bcl-2), inflammation (NF-κB and IL-6), and a decrease in renal reabsorption (AQP2) levels. In the evaluation of the findings obtained in this study, it was determined that the favipiravir or metabolites caused liver and kidney damages.

Neuroprotective Effects of Lacosamide in Experimental Peripheral Nerve Injury in Rats : A Prospective Randomized and Placebo-Controlled Trial.

OBJECTIVE: To evaluate the neuroprotective effects of lacosamide after experimental peripheral nerve injury in rats. METHODS: A total of 28 male wistar albino rats weighing 300-350 g were divided into four groups. In group I, the sciatic nerve exposed and the surgical wound was closed without injury; in group II, peripheral nerve injuries (PNI) was performed after dissection of the nerve; in group III, PNI was performed after dissection and lacosamide was administered, and in group IV, PNI was performed after dissection and physiological saline solution was administered. At 7 days after the injury all animals were sacrificed after walking track analysis. A 5 mL blood sample was drawn for biochemical analysis, and sciatic nerve tissues were removed for histopathological examination. RESULTS: There is low tissue damage in lacosamide treated group and antioxidant anzymes and malondialdehyde levels were higher than non-treated and placebo treated group. However there was no improvement on clinical assessment. CONCLUSION: The biochemical and histological analyses revealed that lacosamide has neuroprotective effect in PNI in rats. This neuroprotective capacity depends on its scavenger role for free oxygen radicals by increasing antioxidant enzyme activity.

Neuroprotective Effects of Lacosamide in Experimental Traumatic Spinal Cord Injury in Rats.

AIM: To evaluate the effects of lacosamide on traumatic spinal cord injury (SCI) in rats. MATERIAL AND METHODS: A total of 28 male Wistar albino rats, each weighing 300-350 g, were included. They were randomly assigned to four groups. In Group 1, only a laminectomy was performed; in Group 2, SCI was performed after laminectomy; in Group 3, SCI was performed after laminectomy followed by lacosamide administration, and in Group 4, SCI was performed after laminectomy followed by physiological saline administration. After 48 hours, all animals were sacrificed, blood samples were drawn, and their spinal cords were removed. The serum levels of catalase, glutathione peroxidase (GPx), superoxide dismutase (SOD) and malondialdehyde (MDA) were measured, and the spinal cord specimens were examined for neuronal degeneration (PND). RESULTS: The MDA level was the lowest and the antioxidant enzyme levels were the highest in Group 3. There were statistically significant differences between Group 3 and the others in their PND score, serum MDA, SOD, GPX and catalase levels (p < 0.05). CONCLUSION: Lacosamide has a neuroprotective effect in SCI in rats that is related to its ability to decrease the production of reactive oxygen species by increasing antioxidant enzyme expression, inhibit lipid peroxidation and attenuate glial cell activation.

The first experimental research on the pathogenicity of Arcobacter butzleri in zebrafish.

This experimental study was conducted to investigate the pathogenicity and histopathology of Arcobacter butzleri in zebrafish model organism. Firstly, mean infective dose (ID50) of A. butzleri was calculated in zebrafish as 1.3×10(8)CFU/mL and 1×10(5)CFU/mL by immersion and intraperitoneal injection, respectively. For histopathological trials, the ID50 of A. butzleri were given to zebrafish by both immersion and intraperitoneal routes and then, clinical and pathological findings were evaluated on days 1, 3, 5, 7 and 21 of the experiment. During the experimental period, no clinical signs or gross lesions of disease were observed in the zebrafish groups infected with the ID50 of A. butzleri by either method. In the histopathological examination, acute inflammation characterized by neutrophil and plasma cells and local necrosis or congestion were determined in liver, kidney, spleen, gaster and other visceral organs. In addition peritonitis, leukocyte infiltration, villous atrophy and septicemia were observed in the experimental groups. Neither gross nor microscopic lesions were detected in the control groups. This study presented the first report of experimental A. butzleri infection in wild zebrafish. In the light of the findings obtained here, it was concluded that zebrafish could be used as a model organism to investigate pathogenicity and histopathology of arcobacters.