The hormonal mechanism of the effects of meperidine, sertraline, tianeptine, and their combinations on reproductive functions in female rats.

BACKGROUND: Infertility caused by drugs that inhibit serotonin reuptake has been attributed to serotonin toxicity. Serotonin has been linked to cause a rise in prolactin and cortisol. This study examined the effects of meperidine, sertraline, tianeptine and combinations on female rat reproductive function. METHODS: Female rats were split into 8 groups (n=7): healthy control (HG), meperidine (MG), sertraline (SG), tianeptine (TG), meperidine+sertraline (MSG), meperidine+tianeptine (MTG), sertraline+tianeptine (STG), meperidine+sertraline+tianeptine (MSTG). Meperidine (20 mg/kg, 2×1) was injected intramuscularly. Sertraline (30 mg/kg, 1×1) and tianeptine (5 mg/kg, 1×1) were given orally. The HG received distilled water as solvent. Treatments continued for 20 days. Then, adult males were added to the rat groups and drug treatment continued for another five days. Blood samples were collected on day 26 for biochemical tests. RESULTS: Total oxidant status (TOS) and total antioxidant status (TAS) were not statistically significant between groups (p>0.05). Meperidine (p<0.001) and sertraline (p<0.001) alone increased prolactin levels in comparison to HG and tianeptine inhibited the increase (p<0.001). While meperidine increased corticosterone levels versus HG (p<0.001), sertraline and tianeptine were close to HG (p>0.05). Number of infertile animals was 6 for meperidine, 3 for sertraline, and none for tianeptine. While the duration of pregnancy in MG (15 days) and SG (15 days) was longer compared to HG (2.86 days), no change was observed in TG (2.5 days). CONCLUSION: Tianeptine and other serotonin re-uptake stimulants may be useful in the treatment of reproductive dysfunction and infertility due to serotonin re-uptake inhibitor treatment.

Protective effect of cinnamon extract against cobalt-induced multiple organ damage in rats.

Background: The role of oxidative stress and inflammation in cobalt (Co) toxicity has been the focus of previous studies. Cinnamon and its main components have been reported to have protective effects in various tissues with antioxidant and anti-inflammatory effects. Aims: In this study, the protective effect of cinnamon extract (CE) against possible Co-induced heart, kidney, and liver damage in rats was investigated biochemically. Methods: Eighteen albino Wistar-type male rats were categorized into three groups (n = 6 per group): control (CG), CoCL2-administered (CoCL2), and CE + CoCL2-administered (CE + Co) groups. The CE + CoCL2 group was administered CE (100 mg/kg), and the CoCL2 and CG groups were administered distilled water orally by gavage. One hour after the administration, Co (150 mg/kg) was administered orally to the CE + CoCL2 and CoCL2 groups. This procedure was repeated once daily for 7 days. Then, biochemical markers were studied in the excised heart, kidney, and liver tissues. Results: CoCL2 increased oxidants and proinflammatory cytokines and decreased antioxidants in heart, kidney, and liver tissues. Heart, kidney, and liver tissue were affected by Co damage. CE treatment suppressed the CoCL2-induced increase in oxidants and proinflammatory cytokines and decrease in antioxidants in heart, kidney, and liver tissues. CE treatment has been shown to attenuate cardiac damage by reducing serum troponin I (TpI) and creatine kinase-MB (CK-MB), renal damage by reducing creatinine and blood urea nitrogen (BUN), and liver damage by reducing alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Conclusion: Co induced the production of oxidants and proinflammatory parameters and antioxidant depletion in heart, kidney, and liver tissues of rats. Our experimental results show that CE protects heart, kidney, and liver tissues against oxidative and inflammatory changes induced by CoCLl2.

Lacidipine, thiamine pyrophosphate and their combination on the ocular ischemic syndrome induced by bilateral common carotid artery ligation.

AIM: To investigate the effect of lacidipine, thiamine pyrophosphate (TPP) and the combination of lacidipine and TPP against oxidative and inflammatory eye damage induced by bilateral common carotid artery ligation in rats. METHODS: Male albino Wistar rats were categorized as those who underwent sham surgery (SG), right and left common carotid cross-clamping and unclamping procedure (CCU), lacidipine+CCU (LCCU), TPP+CCU (TCCU), and combination of lacidipine and TPP (LTC)+CCU (LTCCU). One hour before anesthesia, the LCCU (n=6) received lacidipine (4 mg/kg, orally) and the TCCU (n=6) received TPP (20 mg/kg, intraperitoneally). The SG (n=6) and CCU (n=6) received the same volume of distilled water from the same route. After anesthesia (60 mg/kg ketamine, intraperitoneally), the necks of the rats were opened in the midline. Ischemia was created for 10min by placing clips on the right and left common carotid arteries. Rats in the SG only underwent subcutaneous incision. After 10min, the clips were removed and reperfusion was achieved for six days. Then, the animals were euthanized (120 mg/kg ketamine, intraperitoneally) and the levels of oxidant, antioxidant and proinflammatory cytokines in the eye tissues were determined. The retinal tissue of the eye was also examined histopathologically. RESULTS: Lacidipine, TPP, and LTC significantly prevent the increase in malondialdehyde, tumor necrosis factor-alpha, interleukin-1ß (IL-1ß), and IL-6 levels, decrease in total glutathione levels, superoxide dismutase and catalase activities and histopathological retinal damage in eye tissue induced by bilateral common carotid artery ligation in rats. The impact of these drugs on protection is determined to be LTC>lacidipine>TPP. CONCLUSION: As a result of the study, it is concluded that LTC may be more effective than lacidipine and TPP alone in treating ocular ischemic syndrome.

Protective Effect of Ramipril Against Oxidant and Proinflammatory Cytokine Damage Induced by Ischemia-Reperfusion in Ovarian Tissue in Rats.

BACKGROUND: It is known that the increase in oxidants and proinflammatory cytokines, as well as the decrease in antioxidants, play a role in ovarian ischemia-reperfusion (I/R) injury. The antioxidant and anti-inflammatory properties of ramipril have been studied in various diseases. This study aims to investigate the effect of ramipril on I/R-induced ovarian damage in rats. METHODS: Rats were divided into healthy (HG), sham (SG), ovary I/R (OIR), and ramipril + ovary I/R (ROIR) groups (n = 6/each group). One hour before the surgical procedures, ROIR was given 2 mg/kg ramipril. The lower abdomen of the SG, OIR, and ROIR was surgically opened. Right ovarian tissues of OIR and ROIR were subjected to 2 hours of ischemia and 6 hours of reperfusion. Then, all animals were euthanized, and their right ovaries were removed. Ovarian tissues were examined for oxidants (malondialdehyde), antioxidants (total glutathione, superoxide dismutase, and catalase), and proinflammatory cytokines (nuclear factor kappa-B, tumor necrosis factor-alpha, interleukin 1 beta, and interleukin-6) analysis was performed. Tissues were examined histopathologically. RESULTS: The ovarian tissue of the OIR, which underwent the I/R procedure, exhibited a significant increase in oxidant and proinflammatory cytokine levels, along with a decrease in antioxidant levels (P < .001). Ramipril suppressed the I/R-induced increase in oxidants and pro-inflammatory cytokines and the decrease in antioxidants (P < .001). Ramipril also attenuated I/R-induced histopathological damage in ovarian tissue (P < .05). CONCLUSION: Ramipril treatment may be a treatment strategy to protect ovarian tissue against oxidative and inflammatory damage of I/R.

Taxifolin as a novel therapeutic agent for epileptic seizures induced by caffeine-induced oxidative stress in rats.

BACKGROUND: Epilepsy is a severe neurological disease that results from excessive and/or synchronized neuronal activity in the brain, and oxidative stress plays a role in its pathogenesis. Taxifolin is a flavonoid that exhibits antioxidant activity. OBJECTIVES: To investigate the effects of taxifolin on caffeine-induced epileptic seizures in rats and reveal the role of antioxidant activity in antiepileptic therapy. MATERIAL AND METHODS: Forty rats were divided into 4 groups (n = 6/group): caffeine 300 mg/kg group (CG), taxifolin 50 mg/kg + caffeine 300 mg/kg group (TCG), 2 mg/kg diazepam + 300 mg/kg caffeine group (DCG), and a healthy group (HG). Taxifolin was given to the TCG, and diazepam was given to the DCG orally. One hour later, caffeine was injected intraperitoneally into the CG, TCG and DCG rats. The time between the caffeine injection and the contractions (the latency period) was determined. Animals were euthanized 1 h after caffeine injection, and brain tissues were biochemically examined for oxidants and antioxidants. RESULTS: Taxifolin and diazepam prolonged the latency period to a similar extent (p = 0.549), while taxifolin was more successful in preventing mortality. Taxifolin suppressed the caffeine-induced increase in myeloperoxidase, total oxidant status and oxidative stress index, and decreased total glutathione, superoxide dismutase and total antioxidant status more effectively than diazepam (p < 0.05). CONCLUSIONS: We showed the relationship between antioxidant activity and epilepsy treatment, and demonstrated that taxifolin may be useful for treating epilepsy.

The Role of Adrenaline, Noradrenaline, and Cortisol in the Pathogenesis of the Analgesic Potency, Duration, and Neurotoxic Effect of Meperidine.

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.

Effects of taxifolin on aspirin-induced gastric damage in rats: macroscopic and biochemical evaluation.

Taxifolin (dihydroquercetin) is a flavanonol isolated from various plants and has antioxidant effects. The aim of our study was to macroscopically and biochemically investigate the effects of taxifolin on aspirin-induced oxidative gastric damage in rats and to evaluate them by comparison with those of famotidine. Rats were divided into four drug administration groups: a healthy control group, an aspirin-only group (ASG), a taxifolin + aspirin group (TASG), and a famotidine + aspirin group (FASG). The results revealed that in light of the results that we obtained, 50 mg/kg taxifolin had anti-ulcer effects. At this dose, taxifolin was able to bring COX-1 activities to a level close to those seen in healthy rats with appropriate macroscopic, oxidant/antioxidant, and biochemical parameters. Based on these results, it can be said that taxifolin may be successfully used as a more potent alternative to famotidine, which is the currently accepted treatment for aspirin-induced ulcers.

Carvacrol prevents acrylamide-induced oxidative and inflammatory liver damage and dysfunction in rats.

Background: Acrylamide causes hepatotoxicity with the effect of oxidative stress and inflammatory processes. Carvacrol is a monoterpenic phenol with antioxidant and anti-inflammatory properties. Aims: To determine the effects of carvacrol on oxidative liver injury induced by acrylamide administration in rats. Methods: Rats were divided into three groups of six animals each: healthy group acrylamide group (ACR), and acrylamide + carvacrol group (TACR). First, carvacrol (50 mg/kg) was administered intraperitoneally to the CACR group. One hour later, acrylamide (20 mg/kg) was given orally to the ACR and CACR groups. This procedure was performed for 30 days, after which the animals were sacrificed. The malondialdehyde (MDA) and total glutathione (tGSH) levels, total oxidant (TOS) and total antioxidant status (TAS), tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1ß), and nuclear factor kappa b (NF-κB) were measured in the excised liver tissues. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were determined in blood serum samples. Liver tissues were also examined histopathologically. Results: In the ACR group, malondialdehyde, TOS, ALT, AST levels, and NF-κB, IL-1ß, and TNF-α levels were found to be high, and tGSH and total antioxidant status levels were low. In addition, diffuse degenerative changes and necrosis in hepatocytes, and moderate inflammation in the portal region were detected in the liver tissues of the ACR group. While carvacrol prevented the biochemical changes induced by acrylamide, it also alleviated the damage in the histological structure. Conclusion: Carvacrol may be used for liver damage caused by acrylamide.

Favipiravir-induced inflammatory and hydropic degenerative liver injury in rats.

BACKGROUND: Favipiravir is very effective in the treatment of many viral infections, especially at high doses. It was used at such doses to treat coronavirus disease 2019 (COVID-19) during the pandemic. However, liver damage was reported in patients undergoing such treatment. OBJECTIVES: This study aimed to investigate the effects of low and high doses of favipiravir on the liver of rats, using biochemical and histopathological methods. MATERIAL AND METHODS: Wistar albino rats were allocated to one of 3 groups, namely a healthy group (HG), a 100 mg/kg favipiravir (FAV-100) group and a 400 mg/kg favipiravir (FAV-400) group. Favipiravir was administered orally at 100 mg/kg and 400 mg/kg doses to the FAV-100 (n = 6) and FAV-400 (n = 6) groups, respectively. Distilled water was administered orally (1 mL) using the same method to the HG (n = 6). This procedure was repeated twice a day for 1 week. At the end of this period, the animals were euthanized with a high dose of thiopental anesthesia (50 mg/kg) and their liver tissues were removed. RESULTS: Favipiravir caused an increase in malondialdehyde (MDA), nuclear factor kappa B (NF-κB) and interleukin 6 (IL-6) levels in the liver tissue, as well as elevated alanine aminotransaminase (ALT) and aspartate aminotransferase (AST) levels in the blood. Moreover, favipiravir caused a decrease in total glutathione (tGSH), superoxide dismutase (SOD) and catalase (CAT) levels. In addition, severe edema, lymphocyte infiltration and hydropic degeneration were observed in the liver tissue of the FAV-400. CONCLUSIONS: High-dose favipiravir caused more significant oxidative and inflammatory damage in the liver tissue of rats than low-dose favipiravir.

Effects of benidipine, paracetamol, and their combination on postoperative and normal tissue pain thresholds.

Introduction: In clinical practice, inadequate pain inhibition leads to increased morbidity and mortality. Increased intracellular calcium, oxidants, and proinflammatory cytokines are known to play a role in the pathogenesis of postoperative pain. Therefore, we investigated the analgesic effects of benidipine, paracetamol, and benidipine-paracetamol combination (BPC) on postoperative and normal pain thresholds in rats. Material and methods: Sixty-four male albino Wistar rats weighing 285-295 g were used. The without-incision rats were divided into 4 subgroups: healthy control, benidipine alone, paracetamol alone, and BPC. The scalpel-incision rats were divided into 4 subgroups: scalpel incision, scalpel incision + benidipine, scalpel incision + paracetamol, and scalpel incision + BPC. Paw pain thresholds of rats were measured using a Basile algesimeter. Biochemical analyses were performed on the paw tissues of 6 rats randomly taken from the experimental groups, each containing 8 rats. Rats were sacrificed immediately after the measurements. After the pain threshold tests were finished, the paw tissues were removed and malondialdehyde (MDA), total glutathione (tGSH), cyclooxygenase (COX), and interleukin-6 (IL-6) levels were measured. Results: There was no significant difference between the groups in paw pain threshold and measured biochemical parameters in rats without incision. The decrease in the pain threshold of the incised paw was also best prevented by BPC, followed by benidipine and then paracetamol. Furthermore, increases in scalpel-incised paw tissue MDA, COX-2, and IL-6 levels and the decrease in tGSH were significantly suppressed by benidipine and BPC, while paracetamol could only significantly inhibit the increase in IL-6 production. Conclusion: The combination of the L-type Ca2+ channel blocker benidipine and paracetamol (BPC) may provide potent analgesia. Our experimental results support that BPC may be useful in the treatment of severe pain that cannot be adequately inhibited by paracetamol.

Effect of low and high dose of favipiravir on ovarian and reproductive function in female rats: Biochemical and histopathological evaluation.

Favipiravir is a drug which shows antiviral activity by inhibiting RNA-dependent RNA polymerase. Favipiravir causes severe adverse effects at high doses. The aim of this study was to investigate the effects of low and high dose favipiravir on ovarian and reproductive function in female rats. The rats were divided into three groups: HG group (healthy rats), FAV-100 group (rats administered 100 mg/kg favipiravir), and FAV-400 group (rats administered 400 mg/kg favipiravir) with 12 rats in each group. Favipiravir was administered orally twice daily for 1 week. Six rats from each group were euthanized and their ovaries were removed. Oxidative and antioxidant parameters were measured in ovarian tissues and examined histopathologically. The remaining animals were kept to breed. Animals receiving favipiravir had increased oxidant content, decreased antioxidant activity, decreased histopathological damage, infertility, and gestational delay. Favipiravir treatment should be used with caution, especially in women of reproductive age.

Beneficial interaction of pycnogenol with indomethacin in rats.

Cyclooxygenase 2 (COX-2) is responsible for the therapeutic effects of indomethacin, while inhibition of the COX-1 enzyme and oxidative stress are responsible for its gastro-toxic effects. It has been reported that pycnogenol increases the expression of COX-1, suppresses the expression rate of COX-2 and oxidative stress. Our aim in this study is to investigate the antiinflammatory activities of indomethacin, pycnogenol, and their combination (PI) in rats and to examine their effects on stomach tissue. In the study, anti-inflammatory activity was investigated in carrageenan-induced inflammatory paw edema in albino Wistar male rats. Effects on stomach tissue were performed by applying the previous method. PI, indomethacin and pycnogenol were the best suppressors of carrageenan inflammation and oxidative stress in paw tissue, respectively. While the groups with the lowest COX-1 activity in paw tissue were IC, PIC and PC, respectively, PIC, IC and PC were the ones that best inhibited the increase in COX-2 activity. Pycnogenol inhibited the increase of malondialdehyde, the decrease of total glutathione and COX-1 in the stomach, and significantly suppressed the formation of indomethacin ulcers. Our experimental results showed that pycnogenol reduced the toxic effect of indomethacin on the stomach and increased anti-inflammatory activity. This beneficial interaction of pycnogenol and indomethacin suggests that PI will provide superior success in the treatment of inflammatory diseases.

Effect of taxifolin on methotrexate-induced oxidative and inflammatory oral mucositis in rats: biochemical and histopathological evaluation.

BACKGROUND: The role of oxidative stress, as well as inflammation in the pathogenesis of methotrexate (MTX)-induced oral mucositis, is a known fact. The anti-inflammatory, antitumor, antimicrobial, and antioxidant properties of taxifolin-the effect we tested against MTX-induced oral mucosal damage-are well known. OBJECTIVE: Evaluating biochemically and histopathologically the effects of taxifolin on methotrexate-induced oral mucosal damage in rats. METHODOLOGY: 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. RESULTS: 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-1ß), 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. CONCLUSION: These findings suggest that taxifolin may be useful to treat MTX-associated oral mucositis.

Effect of tocilizumab on ischemia-reperfusion-induced oxido-inflammatory renal damage and dysfunction in rats.

Ischemia-reperfusion-induced (I/R) renal damage is a pathogenic process that starts with ischemia, then progresses through oxidative stress and inflammation. Tocilizumab (TCZ), a recombinant human monoclonal antibody produced against the IL-6 receptor, will be tested against renal I/R injury. TCZ is known to lower the levels of proinflammatory cytokines and oxidant mediators while raising the amounts of antioxidant molecules. Our purpose is to evaluate the biochemical and histological effects of TCZ against I/R-induced oxido-inflammatory kidney damage and dysfunction in rats. Animals were divided into 3 groups as renal I/R (RIR), I/R+ TCZ (IRT), and healthy group (HG). TCZ was administered at a dose of 8 mg/kg to the IRT group (n=6) of the animals, and distilled water as a solvent was administered intraperitoneally (ip) to the RIR (n=6) and HG (n=6) groups. Then, two hours of ischemia and six hours of reperfusion were applied to the left kidneys of IRT and RIR animals. TCZ significantly inhibited the increase in the levels of malondialdehyde (MDA), nuclear kappa B (NF-κB), tumour necrosis factor alpha (TNF-α), interleukin 1-ß (IL-1ß), IL-6, creatinine (Cr) and blood urea nitrogen (BUN) and decrease in total glutathione (tGSH) with I/R in renal tissue. TCZ also attenuated severe histopathological damage due to I/R in renal tissue. TCZ protected renal tissue from I/R-induced oxidative and inflammatory damage. These results indicate that TCZ may be useful in the treatment of renal I/R injury.

Effect of taxifolin on cyclophosphamide-induced oxidative and inflammatory bladder injury in rats.

The role of oxidative stress and inflammation in the pathogenesis of cyclophosphamide-related side effects has been demonstrated in previous studies. This study aimed to investigate the effect of taxifolin, due to its antioxidant and anti-inflammatory properties, on cyclophosphamide-induced oxidative and inflammatory bladder injury in albino Wistar rats. The taxifolin+cyclophosphamide (TCYC) group was given 50 mg/kg of taxifolin orally by gavage. Normal saline was used as a solvent for the cyclophosphamide (CYC) group and the healthy control (HC) group. One hour after taxifolin administration, 75 mg/kg of cyclophosphamide was intraperitoneally injected in the TCYC and CYC groups. This procedure was repeated once a day for 30 days. At the end of this period, biochemical markers were studied in the excised bladder tissues and histopathological evaluations were conducted. In the histopathological evaluation of the CYC group, severe epithelial irregularity, dilatation, congestion, and polymorphonuclear leukocyte accumulation in the vascular structures were observed. Additionally, the malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6) levels, the total oxidant status (TOS), and the oxidative stress index (OSI) values were significantly higher, and the total glutathione (tGSH) levels and total antioxidant status (TAS) were significantly lower in the CYC group in comparison to the HC group (P<0.001). Taxifolin reduced the cyclophosphamide-induced increases in the MDA, TNF-α, IL-1ß, and IL-6 levels and the TOS and OSI values; it decreased the tGSH and TAS levels and reduced histopathological damage (P<0.001). Taxifolin may be useful in the treatment of cyclophosphamide-induced bladder damage.

The effects of taxifolin on neuropathy related with hyperglycemia and neuropathic pain in rats: A biochemical and histopathological evaluation.

BACKGROUND: 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. OBJECTIVES: To investigate the effects of taxifolin, which has antioxidant and neuroprotective effects, on alloxan-induced hyperglycemia-induced neuropathy and neuropathic pain, biochemically and histopathologically. MATERIAL AND METHODS: 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. RESULTS: 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. CONCLUSIONS: Our experimental results indicate that taxifolin alleviates alloxan-induced hyperglycemia-related neuropathy and neuropathic pain.

Effect of taxifolin on methotrexate-induced oxidative and inflammatory oral mucositis in rats: biochemical and histopathological evaluation

Abstract The role of oxidative stress, as well as inflammation in the pathogenesis of methotrexate (MTX)-induced oral mucositis, is a known fact. The anti-inflammatory, antitumor, antimicrobial, and antioxidant properties of taxifolin—the effect we tested against MTX-induced oral mucosal damage—are well known. Objective Evaluating biochemically and histopathologically the effects of taxifolin on methotrexate-induced oral mucosal damage in rats. Methodology 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. Results 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. Conclusion These findings suggest that taxifolin may be useful to treat MTX-associated oral mucositis.

Effect of Taxifolin on Ischemia/Reperfusion-Induced Oxidative Injury of Sciatic Nerve in Rats.

BACKGROUND: Ischemia is a condition in which blood flow to tissues is decreased or entirely stopped for various reasons. The reperfusion process exacerbates damage caused by ischemia in the organs and tissues. Reactive oxygen species (ROS) are mainly responsible for ischemia-reperfusion (IR) damage. ROS increase results in lipid peroxidation (LPO) and oxidative stress. In the literature, taxifolin reportedly suppresses ROS production. This study aimed to determine the effect of taxifolin, which is a flavonoid, on IR injury of the sciatic nerve in rats. METHODS: This study divided 30 albino Wistar rats into 3 groups: IR without medication (IR) group, taxifolin applied IR (TAX+IR) group, and only dissection made to the sciatic nerve sham group (SHAM). Sciatic nerve injury was induced by applying 2 hours of ischemia and 3 hours of reperfusion to the abdominal aorta and iliolumbar arteries. Biochemical and histopathologic investigations then were performed on sciatic nerve tissues. Malondialdehyde, total glutathione, glutathione reductase, and glutathione peroxidase were analyzed as oxidative stress markers, and tumor necrosis factor-α and interleukin-1ß levels were evaluated as inflammatory stress markers in biochemical tests. RESULTS: The IR group has statistically significantly high oxidant and cytokine levels and low antioxidant levels compared with the TAX+IR group. Taxifolin treatment was also shown to cause significant histopathologic improvement. CONCLUSIONS: We suggest that taxifolin may be effective in preventing IR injury of the sciatic nerve.