Protective effects of topiramate on acetic acid-induced colitis in rats through the inhibition of oxidative stress.

Ulcerative colitis is an intestinal inflammatory condition characterized by a rise in inflammatory mediator production and oxidative stress. Topiramate is an anticonvulsant agent with effectiveness on a wide range of seizures, which is anti-oxidative. This study aims to examine the protective effects of topiramate on acetic acid-induced ulcerative colitis in rats. Rats were randomly divided into four groups as follows: control, acetic acid, acetic acid + topiramate, and acetic acid + dexamethasone groups. Topiramate (100 mg/kg/day) or dexamethasone (2 mg/kg/day) was administered for six consecutive days, and ulcerative colitis was induced on the first day of the study by transrectal administration of 4% acetic acid. Four hours after the last dose of treatments, animals of each group were sacrificed, and colon tissues were removed for further macroscopic, histopathologic, and biochemical analyses. Treatment with topiramate markedly decreased colonic lesions and macroscopic scores as well as the improvement of histopathologic changes. Topiramate also effectively decreased the levels of malondialdehyde and upregulated the activity of anti-oxidative enzymes, including catalase, superoxide dismutase, and glutathione peroxidase. Our results reveal that the administration of topiramate ameliorates acetic acid-induced colitis in rats via anti-oxidative properties, and further studies may introduce it as an effective therapeutic candidate to decrease ulcerative colitis severity.

Biochemical and histopathological evidence for beneficial effects of Empagliflozin pretreatment on acetic acid-induced colitis in rats.

BACKGROUND: Ulcerative Colitis (UC) is a disorder which oxidative stress plays a critical role in its pathogenesis. Empagliflozin (EMPA) is a sodium-glucose cotransporter-2 (SGLT2) inhibitor that has been shown to have anti-inflammatory and antioxidative effects. The aim of this study was to investigate the protective effects of EMPA on acetic acid (AA) induced colitis in rats. METHODS: A total of twenty-four rats were divided into four groups (six animals in each group) as follows: (1) Control group; (2) acetic acid (AA)-induced colitis group (AA); (3) EMPA treatment group (AA + EMPA); (4) Dexamethasone (Dexa) treatment group (AA + Dexa). Animals in pre-treatment groups received EMPA (10 mg/kg, i.p.) or dexamethasone (4 mg/kg, i.p. as reference drug) for four consecutive days before induction of colitis by intra-rectal acetic acid (4% v/v) administration. Twenty-four hours after AA administration, rats were sacrificed and the colon tissues were removed for histopathological and biochemical evaluations. RESULTS: Pretreatment with EMPA significantly decreased colon weight/length ratio (81.00 ± 5.28 mg/cm vs. 108.80 ± 5.51 mg/cm) as well as, macroscopic (2.50 ± 0.57 vs. 3.75 ± 0.25) and histological scores (3.3 ± 0.14 vs. 1.98 ± 0.14) compared to the AA-induced colitis group (p < 0.01). Pretreatment with EMPA significantly reduced malondialdehyde (MDA) (324.0 ± 15.93 vs. 476.7 ± 32.26 nmol/mg p < 0.001) and increased glutathione level (117.5 ± 4.48 vs. 94.38 ± 3.950 µmol/mg, p < 0.01) in comparison to the AA-induced colitis group. Furthermore, a significant increase in catalase (44.60 ± 4.02 vs.14.59 ± 2.03 U/mg, P < 0.01), superoxide dismutase (283.9 ± 18.11 vs. 156.4 ± 7.92 U/mg, p < 0.001), and glutathione peroxidase (10.38 ± 1.45 vs. 2.508 ± 0.37, p < 0.01) activities were observed by EMPA pretreatment when compared to the AA-induced colitis group. These results were in line with those of the reference drug. CONCLUSIONS: It is concluded that EMPA could effectively reduce the severity of tissue injury in experimental colitis. This protective effect may be related to the antioxidative effects of EMPA drug.

Protective effects of sitagliptin on methotrexate-induced nephrotoxicity in rats.

Methotrexate (MTX), a cytotoxic chemotherapeutic and immunosuppressant agent, is widely used in the treatment of autoimmune diseases and different types of cancers. However, its use has been limited by its life-threatening side effects, including nephrotoxicity and hepatotoxicity. The purpose of this study was to investigate the protective effect of sitagliptin on methotrexate (MTX)-induced nephrotoxicity in rats. Twenty-four rats were divided into four groups: control group, which received the vehicle for 6 days; MTX group, which received a single dose of MTX, followed by five daily doses of vehicle dosing; MTX + sitagliptin group, which received a single dose of MTX 1 h after the first sitagliptin treatment and six daily doses of sitagliptin; and sitagliptin group, which received sitagliptin for 6 days. Both MTX and sitagliptin were given as intraperitoneal injections at a dose of 20 mg/kg body weight. All rats were euthanized on the seventh day of the study. Kidney tissues were harvested and blood samples were collected. Serum levels of blood urea nitrogen (BUN) and creatinine were evaluated. Furthermore, catalase, glutathione peroxidase, superoxide dismutase activities, and malondialdehyde (MDA) levels were determined in kidney tissue. In addition, histopathological analysis was conducted. Histopathological evaluation showed that MTX-induced marked kidney injury. Biochemical analysis revealed a significant increase of BUN and creatinine in the serum of the MTX group. Furthermore, oxidative stress and depressed antioxidant system of the kidney tissues were evident in the MTX group. Sitagliptin did not affect these endpoints when administered alone, but it significantly attenuated the observed MTX-induced effects. These results suggest that sitagliptin exhibits potent anti-oxidant properties against the nephrotoxicity induced by MTX in rats.

An overview of possible pivotal mechanisms of Genistein as a potential phytochemical against SARS-CoV-2 infection: A hypothesis.

The Coronavirus Disease 2019 (COVID-19) pandemic has been caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It is a global problem that humanity has not yet found a definitive solution for it. In this regard, a global effort has been done to find effective or potential adjuvant therapies in order to fight this infection. Genistein is a small, biologically active phytoestrogen flavonoid that is found in high amounts in soy and plants of the Fabaceae family. This important compound is known due to its anti-cancer, anti-inflammatory, and antioxidant effects. Additionally, protective effects of genistein have been reported in different pathological conditions through modulating intracellular pathways such as PI3K, Akt, mTOR, NF-κB, PPARγ, AMPK, and Nrf2. Scientific evidence suggests that genistein could have a potential role to treat COVID-19 through its anti-inflammatory and anti-oxidant effects. Furthermore, it appears to interfere with intracellular pathways involved in viral entry into the cell. This review provides a basis for further research and development of clinical applications of genistein as a potential alternative therapy to decrease inflammation and oxidative stress in COVID-19 patients. PRACTICAL APPLICATIONS: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiological agent for the Coronavirus Disease 2019 (COVID-19), has brought unprecedented untold hardship to both developing and developed countries. The inflammation, cytokine storm, and oxidative stress have an important role in the pathogenesis of this infection. In this regard, finding plant-derived compounds with anti-inflammatory and anti-oxidative effects would be very beneficial in reducing the mortality induced by this infection. Genistein an isoflavone derived from soy-rich products possesses versatile biological activities. It has potent anti-inflammatory and anti-oxidative and immunomodulatory effects. Furthermore, this compound may prevent viral entry to host cells and reduce SARS-CoV2-induced lung injury. Therefore, we suggest further studies on the effects of genistein on SARS-Cov-2 infection.

The Promising Effect of Topiramate on Random-Pattern Skin Flap Survival in Rats.

BACKGROUND: Partial necrosis of skin flaps following plastic and reconstructive surgeries is one of the major problems in these medical interventions. This study was conducted to evaluate the beneficial effects of topiramate an anti-epileptic agent on ischemic random skin flaps. MATERIALS AND METHODS: Twenty-four Wistar rats were provided and randomly divided into four experimental groups (control group and low-, intermediate- and high-dose treatment groups). A rat random-pattern skin flap model was performed in all groups, and animals in the low-, intermediate- and high-dose experimental groups were administered topiramate intraperitoneally at doses of 25, 50 and 100 mg/kg, respectively, 1 h before raising the flap and once daily for 7 consecutive days after the initial surgical procedure. Control rats received vehicle according to the same schedule. On postoperative day 7 the flap necrotic area was measured, and tissue samples were stained with hematoxylin and eosin for histological analysis. Furthermore, the oxidative stress in flap tissue was assessed by measuring the activity of superoxide dismutase (SOD), glutathione (GSH) level and the content of malondialdehyde (MDA). RESULTS: Treating animals with 50 and 100 mg/kg topiramate significantly decreased the necrotic flap areas as compared to the control group. Histological studies demonstrated that in intermediate and high dose topiramate groups the inflammatory cell numbers were attenuated and microvessel development were markedly increased. Furthermore, the MDA contents were significantly reduced and GSH levels were significantly increased in these groups as compared to the control group. However, the SOD activity was increased significantly only in high-dose group as compared to the control group. CONCLUSIONS: These findings indicated that topiramate in doses of 50 and 100 mg/kg increases random skin flap survival. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Gastroprotective effect of topiramate on indomethacin-induced peptic ulcer in rats: Biochemical and histological analyses.

Topiramate is an anticonvulsant drug effective against a wide range of seizures and epilepsies. The present study was conducted to investigate the possible protective effect of topiramate on indomethacin-induced gastric mucosal damage in rats. The animals were randomly distributed into four experimental groups with 10 animals in each group. Group 1 was the control group received vehicle only (DMSO at 1:4 (w/v)), group 2 was the model group received indomethacin (50 mg/kg; i.p.), and groups 3 and 4 received topiramate (100 mg/kg; i.p.) and ranitidine (100 mg/kg; i.p.), respectively, 1 h before indomethacin (50 mg/kg; i.p.). The efficacy of topiramate was compared with ranitidine. Animals were euthanized 4 h after indomethacin administration, and gastric tissues were collected for macroscopical, histopathological, and biochemical analyses. The mucosal lesions in the gastric corpus were evaluated by pathological examinations. The results revealed that the administration of indomethacin caused evident gastric mucosal damage with morphological and histological manifestation, whereas topiramate pretreatment extensively ameliorated the gastric injuries. Topiramate pretreatment also reduced the contents of tissue malonaldehyde, enhanced ferric reducing antioxidant power value and glutathione levels, and increased the activity of superoxide dismutase, catalase, and glutathione peroxidase in gastric mucosa compared to the model group. Our results indicate that topiramate might possess a protective role against indomethacin-induced gastric ulcers by inhibition of oxidative stress in gastric tissue.