SUMMARY OBJECTIVE: We aimed to determine whether vitamin C has a protective effect on cisplatin-induced neuropathy in rats. METHODS: In total, 24 rats were included in the study of which 8 rats (no drug administered) were categorized as the control group. The remaining 16 rats were given a total dose of 20 mg/kg cisplatin to induce neuropathy. These drug-administered rats (16 rats) were randomly divided into two groups, namely, group-1 (n=8): cisplatin+saline and group-2 (n=8): cisplatin+vitamin C (500 mg/kg/day). All rats were tested for motor function and electromyographic activity 3 days after cisplatin. Motor performance was evaluated by an inclined-plane test. Compound muscle action potential was evaluated. Plasma malondialdehyde, glutathione, tumor necrosis factor-α, interleukin 6, and sciatic nerve HSP 70 levels were measured. Axon diameter and nerve growth factor expression levels were analyzed. RESULTS: Plasma malondialdehyde, tumor necrosis factor-α, and interleukin 6 levels were higher in the cisplatin+saline group than control group (p<0.001). But vitamin C significantly reduced malondialdehyde and inflammatory cytokine levels when compared with the cisplatin+saline group (p<0.001). Glutathione levels were lower in both cisplatin+saline and cisplatin+vitamin C groups than control group, but vitamin C significantly ameliorated the glutathione levels (p<0.05). Sciatic heat shock protein-70 levels were significantly higher in the cisplatin+vitamin C group than cisplatin+saline group. Compound muscle action potential amplitude and inclined plane test scores were significantly improved in the vitamin C group (p<0.05). Axon diameter and nerve growth factor expression ameliorated with vitamin C (p<0.05). CONCLUSIONS: We demonstrated the ameliorated effects of vitamin C on cisplatin-induced neuropathy through increased heat shock protein-70, nerve growth factor levels, and reduced inflammatory and oxidant effects. The results are promising to improve the neurotoxic effects of cisplatin in cancer patients.

Abstract Purpose To examine the therapeutic effect of external adenosine on an acetic acid-induced acute ulcerative colitis model in rats. Methods Thirty male mature rats were divided into three groups as control, acute colitis (AC) and AC+adenosine group (AC+AD). AC was induced by rectal administration of 4% acetic acid (AA). 5mg/kg/day adenosine was performed i.p for 4 weeks to AC+AD group. Rectum and colon were excised for microscopic and histopathological histopathologic evaluations, and immunohistochemical analysis of nuclear factor kappa B (NF-kB). Blood samples were collected for biochemical detection of TNF-α, Pentraxin-3 and malondialdehyde (MDA) levels. Results AC group had generalized hyperemia and hemorrhage with increased macroscopic and histopathological scores compared with control (P <0.0001) while adenosine treatment decreased these scores significantly (P <0.001), with reduced distribution of disrupted epithelium, leukocyte infiltrates, and focal hemorrhage. AC group showed significantly increased immunoexpression of NF-kB in rectum, plasma and tissue levels of TNF-α, plasma Pentraxin-3 and MDA levels (P <0.0001) while adenosine reduced these levels (P < 0.05). Conclusion Adenosine appears to promote healing of colon and rectum exposed to AA-induced AC, suggesting a boosting effect of adenosine on the intestinal immune system to cure ulcerative colitis.

Fundamento: Pazopanibe (PZP) pode induzir prolongamento da repolarização cardíaca e efeitos pró-arrítmicos, à semelhança de outros inibidores da tirosina quinase. Objetivos: Demonstrar prolongamento da repolarização cardíaca e efeitos eletrofisiológicos pró-arrítmicos induzidos pelo PZP, assim como investigar possíveis efeitos de metoprolol e diltiazem na prevenção de alterações no ECG (prolongamento do intervalo QT) em um modelo experimental em ratos. Métodos: Ratos Sprague-Dawley adultos machos (24) foram designados de modo aleatório para quatro grupos (n = 6). O primeiro grupo (normal) recebeu 4 ml de água da torneira, enquanto os demais receberam 100 mg/kg de PZP (comprimido de Votrient®) através de sonda orogástrica. Após 3 horas, os animais receberam por via intraperitoneal: solução salina, para o grupo normal e para o segundo grupo (controle-PZP+SP); 1 mg/kg de metoprolol (Beloc, Ampola, AstraZeneca), para o terceiro grupo (PZP+metoprolol); e 1mg/kg de diltiazem (Diltiazem, Mustafa Nevzat), para o quarto grupo (PZP+diltiazem). Uma hora após a administração desses medicamentos, e sob anestesia, calculou-se o intervalo QTc registrando-se o ECG em DI. Resultados: Os valores médios do intervalo QTc foram: grupo normal, 99,93 ± 3,62 ms; grupo controle-PZP+SP, 131,23 ± 12,21 ms; grupo PZP+metoprolol, 89,36 ± 3,61 ms; e grupo PZP+diltiazem, 88,86 ± 4,04 ms. Os grupos PZP+metoprolol e PZP+diltiazem apresentaram intervalos QTc significativamente mais curtos comparados aos do grupo controle-PZP+SP (p < 0,001). Conclusão: Ambos metoprolol e diltiazem evitaram o prolongamento do intervalo QT induzido por PZP. Tais medicamentos podem ser uma promissora estratégia para evitar o prolongamento do intervalo QTc associado ao uso de inibidores da tirosina quinase.

Background: Pazopanib (PZP) may induce prolonged cardiac repolarization and proarrhythmic effects, similarly to other tyrosine kinase inhibitors. Objectives: To demonstrate PZP-induced prolonged cardiac repolarization and proarrhythmic electrophysiological effects and to investigate possible preventive effects of metoprolol and diltiazem on ECG changes (prolonged QT) in an experimental rat model. Methods: Twenty-four Sprague-Dawley adult male rats were randomly assigned to 4 groups (n = 6). The first group (normal group) received 4 mL of tap water and the other groups received 100 mg/kg of PZP (Votrient® tablet) perorally, via orogastric tubes. After 3 hours, the following solutions were intraperitoneally administered to the animals: physiological saline solution (SP), to the normal group and to the second group (control-PZP+SP group); 1 mg/kg metoprolol (Beloc, Ampule, AstraZeneca), to the third group (PZP+metoprolol group); and 1mg/kg diltiazem (Diltiazem, Mustafa Nevzat), to the fourth group (PZP+diltiazem group). One hour after, and under anesthesia, QTc was calculated by recording ECG on lead I. Results: The mean QTc interval values were as follows: normal group, 99.93 ± 3.62 ms; control-PZP+SP group, 131.23 ± 12.21 ms; PZP+metoprolol group, 89.36 ± 3.61 ms; and PZP+diltiazem group, 88.86 ± 4.04 ms. Both PZP+metoprolol and PZP+diltiazem groups had significantly shorter QTc intervals compared to the control-PZP+SP group (p < 0.001). Conclusion: Both metoprolol and diltiazem prevented PZP-induced QT interval prolongation. These drugs may provide a promising prophylactic strategy for the prolonged QTc interval associated with tyrosine kinase inhibitor use.