Evaluating biochemically and histopathologically the effects of taxifolin on methotrexate-induced oral mucosal damage in rats. In the taxifolin+MTX (TMTX) group, 50 mg/kg taxifolin was orally administered to rats by gavage. In the MTX and healthy (HG) groups, normal saline was applied to rats as solvent by the same method. One hour after administration of taxifolin and solvent, 5 mg/kg MTX was orally administered to rats in the MTX and TMTX groups. Taxifolin and methotrexate were administered once a day for 30 days. Macroscopic, biochemical, and histopathological evaluations were performed on the inner cheek and tongue tissues of rats. These parts were removed after rats were killed with a high-dose anesthesia. Taxifolin with MTX prevented the increase in oxidant and pro-inflammatory parameters, such as malondialdehyde (MDA), tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1β), interleukin 6 (IL-6), on the inner cheek and tongue tissues of rats. Moreover, taxifolin antagonized the decrease in total glutathione (tGSH). Taxifolin decreased MTX-induced histopathological damage. These findings suggest that taxifolin may be useful to treat MTX-associated oral mucositis.

Oxidative stress refers to the deterioration of the balance between oxidants and antioxidants in favor of oxidants, and this may lead to disruptions in redox signaling and control and/or damage at the molecular level. The presence of low levels of reactive oxygen species (ROS) plays a physiological role in intracellular signaling pathways. However, damage may occur in cells and tissues as a result of excessive increase in ROS production. Because ROS have the potential to damage almost all structures in the cell, including lipid, protein, deoxyribo nucleicacid (DNA). The main source of free radicals in the cell is mitochondria. ROS formation is a natural consequence of oxidative phosphorylation resulting in ATP production in mitochondria. The attack of these radicals results in damage to the mitochondria, a decrease in the activity of oxidative phosphorylation enzymes and consequently a decrease in ATP synthesis. On the other hand, ATP is needed for antioxidant synthesis, which is necessary for cell defence against increasing ROS. Therefore, a decrease in ATP levels makes tissues vulnerable to oxidative stress. In this case, it is likely that tissues exposed to oxidative stress will also have problems in ATP production and the decrease in ATP synthesis will further increase oxidative damage.

Hepatotoxicity of pyrazinamide, an antituberculosis drug, limits its therapeutic use and oxidative stress has been implicated in this toxicity. This study investigated the protective effects of adenosine triphosphate (ATP), thiamine pyrophosphate (TPP), melatonin, and Liv-52, which have previously been shown antioxidant activities, on pyrazinamide-induced hepatotoxicity. 36 albino Wistar male rats were divided into randomized six groups; healthy (HG), pyrazinamide (PZG), ATP + pyrazinamide (APZG), TPP + pyrazinamide (TPZG), melatonin + pyrazinamide (MPZG) and Liv-52 + pyrazinamide (LPZG) groups. ATP 4 mg/kg and TPP 25 mg/kg were administered intraperitoneally (IP). Melatonin 10 mg/kg and Liv-52 20 mg/kg were given orally. One hour after administration of ATP, TPP, melatonin, and Liv-52, 250 mg/kg pyrazinamide was applied orally to all rats except HG group. The treatment was repeated (1 × 1) for 4 weeks. Then, blood samples were taken for determination of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities. Immediately after, the rats were euthanized with thiopental sodium (50 mg/kg, IP), and the livers were removed. The tissues were analyzed for malondialdehyde (MDA), total glutathione (tGSH), superoxide dismutase (SOD), and catalase (CAT) also hydropic degeneration, necrosis, and apoptosis (caspase 3) were examined.One-Way ANOVA was used in biochemical analyses and Tukey test was used as post-hoc. For histopathological and immunohistochemical analysis, the Kruskal-Wallis test was used and Dunn’s test as a post-hoc. Pyrazinamide increased MDA land decreased tGSH, SOD, and CAT levels in liver tissues (p < 0.001). It also increased serum ALT and AST activities and caused severe hydropic degeneration and necrosis in liver tissue (p < 0.001). ATP, TPP, melatonin, and Liv-52 significantly prevented the biochemical and histopathological changes induced by pyrazinamide (p < 0.05). On the other hand, Liv-52 was more successful than other potential protectors in protecting liver tissue from pyrazinamide damage (p < 0.05). ATP, TPP, melatonin, and Liv-52 can be used to protect liver tissue from pyrazinamide-induced hepatotoxicity in rats.

Background and Objectives: The purpose of the study was to investigate the role of adrenaline (ADR), noradrenaline (NDR), and cortisol in the pathogenesis of the analgesic potency, duration, and epilepsy-like toxic effect of meperidine. Materials and Methods: The experimental animals were separated into 11 groups of six rats. In the meperidine (MPD) and metyrosine + meperidine (MMPD) groups, paw pain thresholds were measured before and after the treatment between the first and sixth hours (one hour apart). In addition, ADR and NDR analyses were performed before and after the treatment, between the first and fourth hours (one hour apart). For the epilepsy experiment, caffeine, caffeine + meperidine, and caffeine + meperidine + metyrapone groups were created, and the treatment was applied for 1 day or 7 days. Groups were created in which caffeine was used at both 150 mg/kg and 300 mg/kg. Epileptic seizures were observed in epilepsy groups, latent periods were determined, and serum cortisol levels were measured. Results: In the MPD group, pain thresholds increased only at the first and second hours compared to pre-treatment, while ADR increased at the third hour, leading to a decrease in pain thresholds. In the MMPD group, the increase in paw pain thresholds at 1 and 6 h was accompanied by a decrease in ADR and NDR. In the caffeine (150 mg/kg) + meperidine group, 1-day treatment did not cause epileptic seizures, while seizures were observed and cortisol levels increased in the group in which treatment continued for 7 days. When cortisol levels were compared between the group in which caffeine (300 mg/kg) + meperidine + metyrapone was used for 7 days and the animals receiving caffeine (300 mg/kg) + metyrapone for 7 days, it was found that cortisol levels decreased and the latent period decreased. Conclusions: The current study showed that if serum ADR and cortisol levels are kept at normal levels, a longer-lasting and stronger analgesic effect can be achieved with meperidine, and epileptic seizures can be prevented.

Hyperglycemia can be considered a determining factor in the development of diabetic neuropathy as well as neuropathic pain. There is a relationship between the excessive production of reactive oxygen species (ROS) and the pathogenesis of diabetic neuropathic pain. Taxifolin, on the other hand, is a flavonoid that has been documented to inhibit ROS production. To investigate the effects of taxifolin, which has antioxidant and neuroprotective effects, on alloxan-induced hyperglycemia-induced neuropathy and neuropathic pain, biochemically and histopathologically. The albino Wistar male rats were divided into 3 groups: healthy group (HG), only alloxan group (AXG) and alloxan+taxifolin group (ATG). Hyperglycemia in animals was caused through intraperitoneal injection of alloxan at a dose of 120 mg/kg. Paw pain thresholds of animals were measured using Basile algesimeter. Sciatic nerve tissues were examined biochemically and histopathologically in order to evaluate neuropathy. Our experimental results revealed that taxifolin significantly prevented the increase of plasma glucose concentration level with alloxan administration, the decrease of the paw pain threshold related to hyperglycemia, the change of oxidant-antioxidant balance in the sciatic nerve tissue in favor of oxidants, and the deterioration of tissue morphology in animals. Our experimental results indicate that taxifolin alleviates alloxan-induced hyperglycemia-related neuropathy and neuropathic pain.

Isoniazid and rifampicin (IRC) have been shown to cause hepa-totoxicity in both clinical and preclinical studies. Oxidative stress and in-flammation have been held responsible for the pathogenesis of IRC-induced hepatotoxicity. Antioxidative and anti-inflammatory effects of thiamine py-rophosphate (TPP) and cinnamon extract (CE) have been shown in previous studies. Therefore, our study investigated the protective effects of TPP and CE on possible liver damage caused by IRC treatment in rats. Twenty-four albino Wistar rats were categorized into four groups: a healthy group (HG), an IRC group (IRG), a TPP+IRC group (TIRG), and a CE+IRC group (CIRG). TPP (25 mg/kg) was administered intraperitoneally to TIRG, while CE (100 mg/kg) was administered orally to CIRG. In IRG, TIRG, and CIRG, isoniazid (50 mg/kg) and rifampicin (50 mg/kg) were administered orally one hour after these treatments. For seven days, this procedure was repeated once a day. After this period, blood samples were taken from the tail veins, and the rats were sac-rificed. The removed liver tissues were analyzed for oxidant, antioxidant, and proinflammatory cytokines and subjected to histopathological evaluation. Serum alanine aminotransferase and aspartate aminotransferase activities were also measured. An increase in malondialdehyde, nuclear factor kappa B, tumor necrosis factor-alpha, interleukin 1 beta, and interleukin-6 levels, a decrease in total glutathione levels, superoxide dismutase and catalase activi-ties, and an increase in alanine aminotransferase and aspartate aminotrans-ferase activities were found with IRC treatment (p<0.001). The histopatho-logical analysis of the IRG suggested hepatotoxicity (p<0.001). TPP and CE administered with IRC inhibited the biochemical changes (p<0.001). In the TIRG, this inhibition was higher than in the CIRG (p<0.05). Histological damage was inhibited by TPP (p<0.001). CE prevented biochemical changes but not histological changes except inflammatory cell infiltration. Therefore, TPP may be better than CE in preventing IRC-induced hepatotoxicity.