Labetalol Ameliorates Experimental Colitis in Rat Possibly Through its Effect on Proinflammatory Mediators and Oxidative Stress.

BACKGROUND: Members of beta blockers drugs possess significant antioxidant activities. The current research is to assess the effect of the labetalol on acetic acid (AA-induced) colitis in rat model. METHODS: Forty adult Wistar rats were separated into 4 groups, including the negative control group, AA group, AA + sulfasalazine (100 mg/kg/day) group, and AA + labetalol (300 mg/kg/day) group. Colitis was induced in rats by the interrectal installation of 2 mL of 4% (v/v) AA. Sulfasalazine and labetalol were administered orally for 7 days after 2 hours of induction. The following parameters were measured: disease activity index (DAI), histopa-thological changes and colon tissue homogenate concentrations of proinflammatory mediators IL-1ß, adhesion molecules ICAM-1, and oxidative stress marker myeloperoxidase (MPO). RESULTS: The treatment with labetalol significantly reduced DAI and histopathological changes induced by AA. Also, labetalol markedly decreased the concentrations of IL-1ß, ICAM-1, and MPO in colonic tissue that were increased by AA. The effects of labetalol were significantly lower than that produced by sulfasalazine as standard drug. CONCLUSIONS: Labetalol exerts ameliorative effects on disease activity and histopathological features of AA-induced colitis in rats possibly through antioxidant effects and inhibition of inflammatory mediators.

Comparative treatment of Sulfasalazine+Ezetimibe combination and Sulfasalazine in a rat model with induced colitis.

Ulcerative colitis is a chronic inflammatory disease with high mortality and morbidity worldwide. It causes inflammation in the lining of the colon, resulting in several symptoms that negatively impact the quality of life. Unfortunately, there is currently no known cure for this condition. Therefore, it is crucial to explore alternative treatment approaches. This research aimed to investigate the anti-inflammatory and antioxidative effects of a combination therapy involving Sulfasalazine+Ezetimibe compared to Sulfasalazine alone in a rat model of ulcerative colitis. Forty adult rats were divided into four groups for this study. The groups consisted of a control group (negative control), an acetic acid group (positive control), an acetic acid+Sulfasalazine (100 mg/kg per day) group, and an acetic acid+Sulfasalazine (50 mg/kg)+Ezetimibe (5 mg/kg) group. Rats were treated for one week, and colitis was induced by administering 2 ml of 4% (v/v) acetic acid inter-rectally. After sacrifice, the colonic tissue homogenate was analyzed for several markers, including proinflammatory cytokines (TNF-α, IL-1ß, NF-κB), oxidative stress markers (malondialdehyde, myeloperoxidase), and adhesive molecule markers (E-selectin, ICAM-1). Sulfasalazine and the combination of Sulfasalazine+Ezetimibe significantly reduced the colonic levels of TNF-α, IL-1ß, NF-κB, MDA, and E-selectin in the homogenate. However, the combination therapy of Sulfasalazine and Ezetimibe demonstrated a superior effect.

Role of Iberin as an anti-apoptotic agent on renal ischemia-reperfusion injury in rats.

Ischemia-reperfusion injury (IRI) is a major contributor to acute and chronic kidney failure, heart failure, and ischemic stroke. This study aimed to investigate the therapeutic potential of Iberin, known for its anti-inflammatory, antioxidant, and antiapoptotic properties, in a rat model of renal IRI. Twenty-four adult male rats were randomly divided into four groups: Group I (Sham group) underwent laparotomy without IRI induction; Group II (Control group) underwent laparotomy followed by renal artery clamping for 30 minutes to induce ischemia, followed by 2 hours of reperfusion; Group III (Iberin treatment group) received a pre-injection of Iberin (15 mg/kg) and underwent 30 minutes of ischemia followed by 2 hours of reperfusion; and Group IV (Vehicle-treated group) received the vehicle (ethanol) 1 hour prior to ischemia and reperfusion induction. Iberin was diluted with ethanol. Biomarkers associated with inflammation, oxidative stress, and apoptosis were measured using enzyme-linked immunosorbent assay. Iberin treatment significantly reduced levels of inflammatory cytokines interleukin-1ß (IL-1ß) and IL-6, Bcl-2-associated X protein (BAX), tumor necrosis factor α (TNF-α), nuclear factor kappa p56, high mobility group B1, and neutrophil gelatinase-associated lipocalin. Moreover, Iberin increased levels of heat shock protein and Bcl2 compared to the control and vehicle groups. Iberin treatment prolonged the ischemic tolerance of renal tissue, potentially preventing or delaying irreversible injuries. These findings highlight the potential of Iberin as a promising candidate for mitigating renal injury caused by ischemia-reperfusion, due to its ability to modulate inflammatory markers.

Protective effect of IAXO-102 on renal ischemia-reperfusion injury in rats.

Ischemia/reperfusion injury (IRI) is a common cause of kidney damage, characterized by oxidative stress and inflammation. In this study, we investigated the potential protective effects of IAXO-102, a chemical compound, on experimentally induced IRI in male rats. The bilateral renal IRI model was used, with 24 adult male rats randomly divided into four groups (N=6): sham group (laparotomy without IRI induction), control group (laparotomy plus bilateral IRI for 30 minutes followed by 2 hours of reperfusion), vehicle group (same as control but pre-injected with the vehicle), and treatment group (similar to control but pre-injected with IAXO-102). We measured several biomarkers involved in IRI pathophysiology using enzyme-linked immunosorbent assay (ELISA), including High mobility group box1 (HMGB1), nuclear factor kappa b-p65 (NF-κB p65), interleukin beta-1 (IL-1ß), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), 8-isoprostane, Bcl-2 associated X protein (BAX), heat shock protein 27 (HSP27), and Bcl-2. Statistical analysis was performed using one-way ANOVA and Tukey post hoc tests. Our results showed that IAXO-102 significantly improved kidney function, reduced histological alterations, and decreased the inflammatory response (IL-1, IL-6, and TNF) caused by IRI. IAXO-102 also decreased apoptosis by reducing pro-apoptotic Bax and increasing anti-apoptotic Bcl-2 without impacting HSP27. In conclusion, our findings suggest that IAXO-102 had a significant protective effect against IRI damage in the kidneys.

Lipopolysaccharide from Rhodobacter spheroids modulate toll-like receptors expression and tissue damage in an animal model of bilateral renal ischemic reperfusion injury.

Ischemic reperfusion injury (IRI) of the kidneys is a direct sequela of surgical procedures associated with the interruption of blood supply. The pathophysiology of IRI is complicated, and several inflammatories, apoptosis, and oxidative stress pathways are implicated. Among the major receptors directly involved in renal IRI are the toll-like receptors (TLRs), specifically TLR2 and TLR4. In this study, we investigated the effects of Lipopolysaccharide from Rhodobacter Sphaeroides (TLR2 and TLR4 antagonist, LPS-RS) and the ultrapure form (pure TLR4 antagonist, ULPS-RS) on the histopathological changes and TLRs expression in an animal model of bilateral renal IRI. Forty-eight adult male rats were allocated into six groups (N=8) as follows: sham group (negative control without IRI), control group (rats underwent bilateral renal ischemia for 30 minutes and 2 hours of reperfusion), vehicle group (IRI+ vehicle), LPS-RS group (IRI+ 0.5 mg/kg of LPS-RS), ULPS-RS group (IRI+ 0.1 mg/kg of ULPS-RS), ULPS-RSH group (IRI+ 0.2 mg/kg of ULPS-RS). Significant improvement in the histopathological damages induced by renal IRI was found in the ULPS-RS treated groups at both doses compared with the control group. The protective effect of ULPS-RS was associated with significantly reduced TLR4 expression without affecting TLR2. Regarding LPS-RS, the tested dose adversely affected the renal tissues as manifested by the histopathological findings, although it similarly affected TLRs expression as ULPS-RS. Our results demonstrated that ULPS-RS was renoprotective while LPS-RS had no protective effect against the tissue damages induced by renal IRI.

GASTROINTESTINAL AND METABOLIC DISTURBANCES IN POST-COVID-19 DISEASE OUTCOMES.

OBJECTIVE: The aim: Recognizing gastrointestinal symptoms that precede COVID-19 respiratory difficulties may be crucial for effective early detection and treatment. PATIENTS AND METHODS: Materials and methods: A total of 200 individuals with the post-covid-19 symptoms for both genders in clinical private and hospital COVID-19 verified by polymerase chain reaction were tracked until they recovered. To evaluate the duration of symptoms as a predictor of COVID-19 prognosis, we proposed a link between gastrointestinal symptoms, metabolic disturbances and disease severity. Glucose disturbances were observed in 65 percent of participants, higher D-Dimer plasma levels have been found in 77 percent of participants, and ferritin plasma levels were found in 62 percent of participants. RESULTS: Results: While gastrointestinal symptoms were common, with nausea accounting for 51% of participants, an increase in appetite accounting for 76% of patients, and anal fissure accounting for 30% of participants. Both metabolic and GIT symptoms disturbances impact a large percentage of men. CONCLUSION: Conclusions: Our conclusion was any patient with covid-19 must need to follow up for at least 1 month after recovery to notified of the post-covid symptoms especially the male gender.

The effect of Niclosamide in acetic acid induce colitis: an experimental study

Ulcerative colitis is an idiopathic chronic inflammatory disease of the colon for which a lot of treatment modalities are present. However, significant side effects are associated with them, and there is a need for a search for other tretment options. This study was aimed to assess the contribution of niclosamide in experimentally established colitis in rats. Animals were categorized into 5 groups; the control group undergoes no induction of UC, colitis group in which UC was induced, and animals receive no treatment, the niclosamide group that received niclosamide and sulfasalazine group that received sulfasalazine. Each group was composed of 10 animals. After the completion of a one-month period of the experiment animals were sacrificed and the following meausres were done: the weight of the colon, determination of the area of mucosal damage by mm2, histological scoring after hematoxylin and eosin stain together with MAC score and immunohistochemistry of IL-6, TNF-alpha, MPO, MDA, CD62, and ICAM1. The results of the current study revealed that Nicosamide was able to reduce the area of mucosal damage, colon weight, histological and Mac scores and immunohistochemical scores of inflammatory and oxidative markers, significantly when contrasted to a group of colitis (P< 0.05). It has been concluded that Niclosamide was proved to have a significant effect as an adjuvant mode of therapy for colitis through its, anti-inflamatory and anti-oxidant effects (AU)

Oxidative stress in patients with Behcet's disease: I correlation with severity and clinical parameters.

The study was designed to investigate the possible correlation between some oxidative stress parameters in Behcet's disease and the clinical manifestations of the disease as well as the possible correlation with the disease severity. Seventy-six patients diagnosed according to the International Study Group criteria for Behcet's disease were included in the study. Sixty patients had mild-to-moderate disease and 16 patients had severe disease. Sixty matched control subjects were also included. After a full history and examination from each subject, 10 mL blood was drawn from each for analysis. Serum malondialdehyde, glutathione, ceruloplasmin, copper and zinc levels were determined. Patients with Behcet's disease showed increased levels of serum malondialdehyde and copper while glutathione and zinc levels were decreased. Comparison between these parameters in patients with mild-to-moderate disease with those with severe disease showed only that serum zinc levels were lower in severe Behcet's disease. Serum malondialdehyde levels were found to be significantly positively correlated with oral ulcer size, duration and frequency. Glutathione levels were found to be inversely correlated with the clinical manifestation index and all oral ulcer parameters. Zinc levels were found to be inversely correlated with the clinical manifestation index and pathergy test positivity grades. Copper levels were found to be positively correlated with oral ulcer number. Although the parameters of oxidative stress did not show correlation with disease severity, they were correlated with the disease manifestations. This points out the importance of oxidative stress in Behcet's disease.

Dapsone in Behçet's disease: a double-blind, placebo-controlled, cross-over study.

The study was designed to investigate the effects of dapsone in the treatment of mucocutaneous manifestations of Behçet's disease and the possible prophylactic role of dapsone in a double blind/placebo controlled clinical trial. Twenty patients diagnosed according to the International Study Group criteria as Behçet's disease were included in the study. Patients were randomly allocated to receive either dapsone 100 mg daily or placebo for three months in a double-blind manner. After three months, patients were crossed over and followed for a further three months. Patients were followed up in each visit by assessing the number, size, duration and frequency of oral and genital ulcers, other cutaneous manifestations, and systemic manifestations of the disease. A pathergy test was done on each visit. Laboratory investigations included hemoglobin concentration, white blood cell count, ESR, and C-reactive protein. In dapsone-treated patients, there were significant reductions in the oral and genital ulcer parameters as well as the incidence of other cutanous and systemic manifestations. In the placebo-treated group, there were no significant changes in these parameters. The pathergy test result as well as those of other laboratory tests were all decreased in the dapsone-treated group. Although this study was a small scale study, it shows that dapsone was effective in treatment of mucocutaneous manifestations of Behçet's disease and possibly in prophylaxis against systemic manifestations of the disease. This result should lead to a larger scale study with a longer duration of follow-up.