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The formation of postoperative intra-abdominal adhesions is a significant challenge in veterinary practice worldwide. Thus, several attempts have been made to identify agents that prevent the occurrence of these postsurgical adhesions. However, finding an ideal and effective agent remains a challenge. Herein, we investigate the potential of tadalafil and tadalafil/cellulose composite as promising therapeutics for preventing postsurgical intra-abdominal adhesions. A cecal abrasion model was established in 30 rats, which either left untreated or treated with tadalafil, cellulose, or tadalafil/cellulose. After 2 weeks, the adhesion formation was evaluated based on gross appearance, oxidative stress markers, pro-inflammatory cytokines, histopathological analysis, and immunohistochemical staining. Compared to the adhesion group, gross and histopathological findings revealed that both the tadalafil and cellulose groups significantly decreased adhesion formation, with better results observed after tadalafil treatment. Importantly the tadalafil/cellulose treatment completely prevented adhesion formation. Additionally, the treated groups showed reduced levels of malondialdehyde (MDA), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6), while increasing the level of reduced glutathione (GSH) compared to the adhesion group. Furthermore, the treated groups reduced the expression of macrophage markers. These findings suggest that the intra-abdominal application of tadalafil and tadalafil/cellulose following abdominal surgery holds promise as a clinical strategy to prevent postsurgical intra-abdominal adhesions, with tadalafil/cellulose demonstrating superior efficacy.

Background Delayed wound closure and non-healing wounds represent a problematic condition with health burden and an economic challenge. Therefore, different strategies have been developed, including skin tissue engineering, which aims to stimulate and support the wound healing process. In this study, the potential of graphene oxide (GO) and chitosan (CTS) biomaterial composite, with and without fetal bovine serum (FBS), was investigated to induce a full-thickness skin wound repair in rats. Methods The GO-CTS composite was characterized using X-ray diffraction, transmission electron microscopy, and Fourier transforms infrared. Cytocompatibility was evaluated via an MTT assay with human endothelial cells (ECs) and mouse embryonic fibroblasts (MEFs) in vitro. The in vivo wound regeneration potential was assessed by creating an 8 mm full-thickness circular skin defect on the dorsal surface of the rat. The defects were randomly divided into control, GO-CTS, FBS, and GO-CTS/FBS groups, and were monitored grossly and histologically at days 7 and 21 after wound induction. Results The GO-CTS material demonstrated high cytocompatibility, with cell viability recorded at 99.2% ± 5.7% for ECs and 110.5% ± 3.9% for MEFs. The highest proliferation rates were observed in the FBS (118.2% ± 2.1%) and GO-CTS/FBS (121.4% ± 4.4%) groups. In vivo, wound closure rates on day 21 were 85.5% ± 0.56% for GO-CTS, 87.5% ± 1.75% for FBS, and 91.5% ± 1.03% for GO-CTS/FBS, all significantly higher than the control group. Additionally, neovascularization, epithelialization, collagen deposition, and granulation tissue formation were more prominent in the treated groups, with skin appendages observed in the GO-CTS/FBS group. Conclusion GO-CTS nanosheets with FBS represent a promising biomaterial for skin tissue engineering and can effectively initiate and support wound healing.

The joint impact of tadalafil (Cilais) as a pharmaceutical residue and microplastics on fish is not well comprehended. The current study examined haematological, biochemical, and antioxidant parameters, along with immunohistochemical and histological indications in tilapia ( Oreochromis niloticus ) after being exposed to tadalafil, polyethylene microplastics (PE-MPs), and their mixtures for 15 days. The fish were distributed into 1st group control group (The fish was maintained in untreated water without any supplements); 2nd group exposed to 10 mg/L PE-MPs;3rd group exposed to 20 mg/l tadalafil (Cilais); 4th group exposed to 20 mg/l tadalafil (Cilais) + 10 mg/LPE-MPs (in triplicate). The levels of creatinine, uric acid, glucose, AST, ALT, and albumin in fish treated with tadalafil alone or in combination with PE-MPs were significantly higher than those in the control group. Fish exposed to PE-MPs, tadalafil, and tadalafil plus PE-MPs showed significantly lower levels of RBCs, Hb, Ht, neutrophils, and lymphocytes compared to the control group. Serum levels of total antioxidant capacity and reduced glutathione (GSH) were notably lowered in fish groups subjected to PE-MPs, tadalafil, and tadalafil + PE-MPs combinations in comparison to the control group. Malondialdehyde (MDA) serum levels were notably elevated in fish groups subjected to PE-MPs, tadalafil, and tadalafil + PE-MPs combinations compared to the control group. The most severe impact was observed in the tadalafil + PE-MPs combination group. Interleukin-6 (IL-6) levels were significantly increased in liver tissues following exposure to both tadalafil and microplastics compared to tissues exposed to only one substance or the control group. Changes in the gills, liver, and renal tissues were seen following exposure to PE-MPs, tadalafil, and tadalafil + PE-MPs combination in comparison to the control group of fish. Ultimately, the mixture of tadalafil and PE-MPs resulted in the most detrimental outcomes. Tadalafil and PE-MPs exhibited showed greater adverse effects, likely due to tadalafil being absorbed onto PE-MPs.

Background Chronic renal failure (CRF) is a progressive loss of renal function that lead to reduced sodium filtration and inappropriate suppression of tubular reabsorption that ultimately leads to volume expansion. The aim of this study was to study the efficacy of furosemide and tadalafil nanoforms compared to conventional forms against adenine-induced CRF rat-model. Methods Addition of 0.75% adenine to the diet of rats for 4 weeks gained general acceptance as a model to study kidney damage as this intervention mimicked most of the structural and functional changes seen in human chronic kidney disease Urine analysis, histopathological changes and immunohistochemical expression of caspase-3 and interleukin-1 beta (IL-1β) in renal tissues were performed. Results Our results showed that the combination of tadalafil and furosemide using conventional and nanoparticle formulations had better renoprotective effect than individual drugs. This was demonstrated by improvement of urinary, serum and renal tissue markers as indicative of organ damage. This was also reflected on the reduction of tubular expression of kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL). Immunohistochemical studies showed that the deteriorated renal cellular changes indicated by increased expression of caspase-3 and IL-1β were greatly improved by the combined treatment particularly with the nanoforms. Conclusions The nanoforms of both furosemide and tadalafil had greater renopreventive effects compared with conventional forms against adenine-induced CRF in rats.

Background Chronic renal failure (CRF) is defined by a significant decline in renal function that results in decreased salt filtration and inhibition of tubular reabsorption, which ultimately causes volume enlargement. This study evaluated the potential renopreventive effects of the NLRP3 inflammasome inhibitor MCC950 in adenine-induced CRF in rats due to conflicting evidence on the effects of MCC950 on the kidney. Methods Since the majority of the kidney tubular abnormalities identified in people with chronic renal disease are comparable to those caused by adding 0.75 percent of adenine powder to a rat's diet each day for four weeks, this method has received broad approval as a model for evaluating kidney damage. Throughout the test, blood pressure was checked weekly and at the beginning. Additionally, oxidative stress factors, urine sample examination, histological modifications, and immunohistochemical adjustments of caspase-3 and interleukin-1 beta (IL-1) levels in renal tissues were carried out. Results Results revealed that MCC950, an inhibitor of the NLRP3 inflammasome, had a renopreventive effect, which was demonstrated by a reduction in blood pressure readings and an improvement in urine, serum, and renal tissue indicators that indicate organ damage. This was also demonstrated by the decrease in neutrophil gelatinase-associated lipocalin tubular expression (NGAL). The NLRP3 inflammasome inhibitor MCC950 was found to significantly alleviate the worsening renal cellular alterations evidenced by increased expression of caspase-3 and IL-1, according to immunohistochemical tests. Conclusion The NLRP3 inflammasome inhibitor MCC950 demonstrated renopreventive effects in the CRF rat model, suggesting that it might be used as a treatment strategy to stop the progression of CRF.

Background Gentamicin (GS) is a potent aminoglycoside antibiotic whose clinical use is limited by nephrotoxicity associated with oxidative stress, mitochondrial dysfunction, and inflammation. This study aimed to explore the renoprotective mechanisms of resmetirom (RES) and curcumin (CUR) against GS-induced renal injury in rats, emphasizing anti-inflammatory and mitochondrial pathways and supporting findings through molecular docking. Methods Twenty-four adult male Wistar rats were randomly allocated into four groups ( n  = 6): control, GS (100 mg/kg, i.p.), GS + CUR (200 mg/kg, oral), and GS + RES (3 mg/kg, oral). Treatments were administered for seven days. Serum renal biomarkers (urea, creatinine) and tissue oxidative stress markers (MDA, NO, GSH) were quantified using spectrophotometric methods. Specific kidney damage indicators for kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) were evaluated. Gene expressions of dynamin-related protein 1 (DRP1) and AKT Serine/Threonine Kinase 1 (AKT1) were analyzed by quantitative RT-PCR, while mammalian target of rapamycin (mTOR) and forkhead box protein O1 (FOXO1) protein expression were assessed immunohistochemically. Histopathological and ultrastructural evaluations were conducted using light and electron microscopy. Molecular docking was performed using AutoDock Vina to assess binding affinities of CUR and RES with AKT1, DRP1, FOXO1, and mTOR. Results GS administration significantly elevated serum urea and creatinine and increased renal MDA levels while decreasing NO and GSH. These alterations were markedly attenuated by CUR and RES, with RES showing superior improvement in renal function and oxidative balance. qPCR analysis revealed significant GS-induced upregulation of AKT1 and DRP1, which was normalized by both CUR and RES. Immunohistochemistry demonstrated downregulation of mTOR and FOXO1 following GS exposure, with substantial restoration after CUR and RES treatments. Histopathological and ultrastructural analyses confirmed the protective effects of both compounds, showing preserved glomerular and tubular integrity. Conclusion Resmetirom and CUR showed significant renoprotective benefits against GS-induced nephrotoxicity by alleviating oxidative stress, modulating mitochondrial dynamics, and restoring cellular signaling pathways involving AKT1, DRP1, mTOR, and FOXO1. The molecular docking results corroborate their direct interactions with these targets, highlighting RES as a promising therapeutic agent for nephroprotection.

Scabies is a contagious skin disease caused by Sarcoptes scabiei mites, posing a significant health risk, especially in poor, crowded settings. Existing treatments are facing challenges due to poor compliance and side effects, necessitating alternative therapies. Hydrogel formulations offer promise by enhancing drug release and bioavailability. This study tested a novel topical ivermectin (IVR) hydrogel for scabies, evaluating its effectiveness, anti-inflammatory, and antioxidant properties. It also assessed treatment outcomes of skin structure and its effect on animal behavior and locomotor activity. IVR hydrogel (1% w/v) was formulated and evaluated based on its physicochemical properties, in vitro release kinetics, and acaricidal activity using a contact bioassay and scanning electron microscopy (SEM). An in vivo bioassay was performed using experimentally infested rabbits treated topically with IVR hydrogel. Treatment efficacy was evaluated via histopathology, oxidative stress, inflammatory and immunological markers, and behavioral changes measured through open-field testing. The IVR gel, at a 100% concentration, achieved complete mite mortality in vitro within 10 minutes, accompanied by extensive cuticular damage. In vivo , treated rabbits exhibited marked clinical improvement, attaining a clinical score near zero (0.17) by day 21, alongside enhanced skin condition and reduced inflammation. The treatment resulted in a statistically significant reduction in inflammatory markers (TNF-α, IL-6, P< 0.001) and oxidative stress (MDA, P< 0.001) without significant alterations in specific immunoglobulin levels (IgG and IgE). Histopathological analysis confirmed improvement of skin architecture, while behavioral assessments revealed no adverse effects on animal behavior. IVR hydrogel demonstrated significant, concentration-dependent acaricidal activity, biocompatibility, and effectiveness in reducing oxidative and inflammatory damage. Based on these findings, topical ivermectin hydrogel may offer a promising platform for further investigation as a treatment modality for scabies.

Acute renal failure (ARF) is a sudden, significant, and often reversible decline in kidney function, with 25% of all hospital-administered pharmaceuticals potentially causing nephrotoxicity. The study investigates the effectiveness of a novel nanoparticle (NP) formulation of glutathione (GSH) and Lepidium sativum (LS) in improving therapeutic outcomes in a rat model of ARF. Sixty adult male albino rats were allocated into ten groups, comprising six rats each, for the study. ARF was created by daily gentamicin (GN) administration for seven consecutive days and various treatment protocols, including chitosan (CS) NPs, spanlastics NPs, as well as conventional, NP formulations of GSH, LS, and their respective combinations. The effect was evaluated through various tests, and properties of nanoparticles were confirmed through characterization processes. The NP compositions markedly enhanced renal function, as seen by reduced urine concentrations of albumin and glucose. Furthermore, the serum concentrations of creatinine (SCr), blood urea nitrogen (BUN), and cystatin C were decreased. Tissue concentrations of nitrite, superoxide dismutase (SOD), and malondialdehyde (MDA), as markers of oxidative stress, were enhanced by both conventional and NP formulations. Additionally, they decreased inflammatory markers such as kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), tumor necrosis factor alpha (TNF-α), and interleukin-6 (IL-6). Histological analysis and immunohistochemical testing revealed that the combination therapy, particularly with the nanoforms, significantly decreased caspase 3 cellular immunoexpression, a sign of kidney cellular damage. The findings show that the ARF renal damage is considerably reduced when NPs containing GSH and LS are administered together. The study suggests a promising pharmacological approach for enhancing kidney regeneration and preserving renal function, potentially aiding in new therapeutic interventions for ARF treatment.

Doxorubicin (DOX) is a commonly used chemotherapeutic medication for treating malignancies, although its cardiotoxicity limits its use. There is growing evidence that alteration of the mitochondrial fission/fusion dynamic processes accompanied by excessive reactive oxygen species (ROS) production and alteration of calcium Ca 2+ homeostasis are potential underlying mechanisms of DOX-induced cardiotoxicity (DIC). Metformin (Met) is an AMP-activated protein kinase (AMPK) activator that has antioxidant properties and cardioprotective effects. The purpose of the study is to assess Met's possible cardioprotective benefits against DOX-induced cardiotoxicity. The study included 32 adult male rats. They were randomly divided into four groups: administered saline, DOX, Met, or DOX combined with Met respectively. Heart tissues were used for biochemical assays that measured oxidative stress markers, malondialdehyde (MDA), reduced glutathione (GSH), mitochondrial dynamics markers, optic atrophy-1(OPA-1) and dynamin-1-like protein (Drp1), calcineurin and caspase-3. Serum levels of myocardial injury markers, cardiac troponin I (cTn-I), and aspartate aminotransferase (AST), were also measured. The results revealed that DOX intoxication was associated with a significant increase in the levels of serum cTn-I and AST, increased cardiac MDA level, increased cardiac Drp1, calcineurin, and caspase-3 expressions, as well as reduced cardiac GSH level and cardiac OPA-1 expression. On the other hand, Met treatment significantly reduced DIC by decreasing oxidative stress, apoptosis, and improving mitochondrial and calcium balance. Finally, this study shows that Met may be able to protect the heart from damage caused by DOX by working as an antioxidant and anti-apoptotic agent and keeping the balance of calcium and mitochondria.

Purpose Urolithiasis, the formation of kidney stones, is a common and severe condition. Despite advances in understanding its pathophysiology, affordable treatment options are needed worldwide. Hence, the interest is in herbal medicines as alternative or supplementary therapy for urinary stone disease. This review explores the use of plant extracts and phytochemicals in preventing and treating urolithiasis. Methods Following PRISMA standards, we systematically reviewed the literature on PubMed/Medline, focusing on herbal items evaluated in in vivo models, in vitro studies, and clinical trials related to nephrolithiasis/urolithiasis. We searched English language publications from January 2021 to December 2023. Studies assessing plant extracts and phytochemicals’ therapeutic potential in urolithiasis were included. Data extracted included study design, stone type, plant type, part of plant used, solvent type, main findings, and study references. Results A total of 64 studies were included. Most studies used ethylene glycol to induce hyperoxaluria and nephrolithiasis in rat models. Various extraction methods were used to extract bioactive compounds from different plant parts. Several plants and phytochemicals, including Alhagi maurorum , Aerva lanata , Dolichos biflorus , Cucumis melo , and quercetin, demonstrated potential effectiveness in reducing stone formation, size, and number. Conclusions Natural substances offer an alternative or supplementary approach to current treatments, potentially reducing pain and improving the quality of life for urolithiasis patients. However, further research is needed to clarify their mechanisms of action and optimize their therapeutic use. The potential of plant-based therapies in treating urolithiasis is promising, and ongoing research is expected to lead to treatment advancements benefiting patients globally.