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Glucagon-like Peptide-1 (GLP-1) receptor agonists (GLP-1RAs) emerged as a primary treatment for type-2 diabetes mellitus (T2DM), however, their multifaceted effects on various target organs beyond glycemic control opened a new era of treatment. We conducted a comprehensive literature search using databases including Scopus, Google Scholar, PubMed, and the Cochrane Library to identify clinical, in-vivo, and in-vitro studies focusing on the diverse effects of GLP-1 receptor agonists. Eligible studies were selected based on their relevance to the varied roles of GLP-1RAs in T2DM management and their impact on other physiological functions. Numerous studies have reported the efficacy of GLP-1RAs in improving outcomes in T2DM, with demonstrated benefits including glucose-dependent insulinotropic actions, modulation of insulin signaling pathways, and reductions in glycemic excursions. Additionally, GLP-1 receptors are expressed in various tissues and organs, suggesting their widespread physiological functions beyond glycemic control potentially include neuroprotective, anti-inflammatory, cardioprotective, and metabolic benefits. However, further scientific studies are still underway to maximize the benefits of GLP-1RAs and to discover additional roles in improving health benefits. This article sought to review not only the actions of GLP1RAs in the treatment of T2DM but also explore its effects on potential targets in other disorders. [ABSTRACT FROM AUTHOR]

Background: To compare kidney blood flow and kidney function tests in infants with hypoxic ischemic encephalopathy (HIE), and the effects of therapeutic hypothermia (TH) during the first 7 days of life. Methods: Fifty-nine infants with HIE were prospectively evaluated. Infants with moderate-severe HIE who required TH were classified as group 1 (n = 36), infants with mild HIE were classified as group 2 (n = 23), and healthy infants were classified as group 3 (n = 60). Kidney function tests were evaluated on the sixth hour, third and seventh days of life in Group 1 and Group 2, and on the sixth hour and third day of life in group 3. Renal artery (RA) Doppler ultrasonography (dUS) was performed in all infants on the first, third, and seventh days of life. Results: Systolic and end diastolic blood flow in RA tended to increase and RA resistive index (RI) tended to decrease with time in group 1 (p = 0.0001). While end diastolic blood flow rates in RA on the third day were similar in patients with severe HIE and mild HIE, it was lower in patients with mild-moderate-severe HIE than healthy newborns. On the seventh day, all three groups had similar values (p > 0.05). Serum blood urea nitrogen (BUN), creatinine, uric acid, and cystatin C levels gradually decreased and glomerular filtration rate (GFR) gradually increased during TH in group 1 (p = 0.0001). Serum creatinine levels gradually decreased while GFR gradually increased during the study period in group 2. Conclusions: Therapeutic hypothermia seems to help restore renal blood flow and kidney functions during the neonatal adaptive period with its neuroprotective properties. [ABSTRACT FROM AUTHOR]

Tuberculosis (TB) is a challenging public health issue, particularly in poor and developing countries. Rifampicin (RIF) is one of the most common first-line anti-TB drugs but it is known for its adverse effects on the hepato-renal system. The present study investigated the efficacy of morin hydrate (MH) in protecting hepato-renal damage inflicted by RIF in rats. RIF (50 mg/kg), and a combination of RIF (50 mg/kg) and MH (50 mg/kg) were administered orally for 4 weeks in rats. Silymarin (50 mg/kg) was used as a positive control. Increased levels of serological parameters such as AST, ALT, ALP, LDH, GGT, bilirubin, triglyceride, total cholesterol, urea, uric acid, creatinine, TNF-α, IFN-γ, IL-6 along with the decreased level of IL-10, total protein and albumin were used as markers of hepatic and renal injury. Oxidative damage in the tissues was measured by the increase in lipid peroxidation and decline in GSH, SOD and catalase activities. Histopathology of liver slices was used to study hepatic architecture. Four-week RIF treatment produced altered serological parameters with an increase in pro-inflammatory cytokines in serum suggesting hepatotoxicity and nephrotoxicity. The antioxidant status of the liver and kidney (increased lipid peroxidation and decline in GSH, SOD and catalase) was compromised. Cellular damage and necrosis were observed in liver slices. MH supplementation with RIF improved hepato-renal functions by restoring the serum and tissue markers towards normal values. Histological observations authenticated the results. MH supplementation also reduced the production of pro-inflammatory cytokines. Thus, the results revealed that MH provides protection against RIF-induced hepato-renal injury. [ABSTRACT FROM AUTHOR]

Cisplatin is an effective chemotherapeutic drug widely used for the treatment of various solid tumors; however, its clinical use and efficacy are limited by its inherent nephrotoxicity. The pathogenesis of cisplatin-induced nephrotoxicity is complex and has not been fully elucidated. Cellular uptake and transport, DNA damage, apoptosis, oxidative stress, inflammatory response, and autophagy are involved in the development of cisplatin-induced nephrotoxicity. Currently, despite some deficiencies, hydration regimens remain the major protective measures against cisplatin-induced nephrotoxicity. Therefore, effective drugs must be explored and developed to prevent and treat cisplatin-induced kidney injury. In recent years, many natural compounds with high efficiency and low toxicity have been identified for the treatment of cisplatin-induced nephrotoxicity, including quercetin, saikosaponin D, berberine, resveratrol, and curcumin. These natural agents have multiple targets, multiple effects, and low drug resistance; therefore, they can be safely used as a supplementary regimen or combination therapy for cisplatin-induced nephrotoxicity. This review aimed to comprehensively describe the molecular mechanisms underlying cisplatin-induced nephrotoxicity and summarize natural kidney-protecting compounds to provide new ideas for the development of better therapeutic agents. [ABSTRACT FROM AUTHOR]

Cadmium (Cd), a non-redox metal, has been described as an environmental toxicant that poses a great threat to human health. Therefore, this study aimed to appraise the mitigating potential of the aqueous extract of Bridelia ferruginea (Bf) stem bark against hepato-renal toxicity in Cd-exposed Wistar rats. Thirty (30) adult male Wistar rats (weight 150–200 g) were randomly grouped into five (5) groups of six (6) rats each (n = 6), and experimental rats received a single treatment of cadmium chloride (CdCl2; 30 mg/kg body weight (bw)). Cd-exposed rats were administered 50, 100, and 200 mg/kg bw aqueous extract of Bf stem bark for 14 days. Cd exposure caused hepato-renal toxicity in the untreated control as revealed by a significant (p < 0.05) increase in the serum liver function markers (i.e., AST, ALT, and ALP) as well as a marked (p < 0.05) decrease in hepatic antioxidant enzymes. A similar effect was also noticed in the renal function biomarkers (i.e., creatinine and urea) and its antioxidant enzymes. However, Cd-exposed groups–administered aqueous extract of Bf stem bark revealed a significant (p < 0.05) decrease in serum activities of AST, ALP, and ALT, as well as a significant (p > 0.05) difference in TP level compared to Cd-induced hepato-renal toxicity untreated and normal control. Similarly, hepatic and renal antioxidant parameters (SOD, CAT, and GSH), TP, serum lipid profile, urea, and creatinine were significantly (p < 0.05) improved among the groups-administered aqueous extract of Bf stem bark compared to Cd-induced hepato-renal toxicity untreated and normal control. The renal and hepatic Cd concentrations of groups administered aqueous extract of Bf stem bark significant (p < 0.05) decrease compared to Cd-induced hepato-renal toxicity untreated and normal control. Likewise, histological examinations of kidney and liver tissues of the groups administered aqueous extract of Bf stem bark revealed restoration of normal architecture. Therefore, aqueous extract of Bf stem bark could be suggested to be hepatoprotective and renoprotective in Cd toxicity. [ABSTRACT FROM AUTHOR]

Gentamicin (GM) is an effective antibiotic against gram-negative bacterial infection. However, GM can produce nephrotoxicity. Stachys lavandulifolia Vahl. (SL) is extensively used in folk medicine as herbal tea and has strong antioxidative effects. The aim of this study was to investigate the protective effect of SL on GM-induced nephrotoxicity in rats. In this study, forty-two male Wistar rats were randomly divided into six equal groups (N = 7 each): control (group I), GM-treated (group II), SL200 mg/kg + GM-treated (group III), SL400 mg/kg + GM-treated (group IV), SL200 mg/kg-treated (group V), and SL400 mg/kg-treated (group VI) groups. The treatment procedures continued for 10 days. At the end of the experiment, serum and the kidneys of all groups were harvested for histological and biochemical examination. No statistical significant improvement in histological and biochemical indices was shown at 200 mg/kg of SL treatment in group III compared with group II; however, at 400 mg/kg of SL, normalized serum levels of uric acid (P < 0.001), urea (P < 0.001), creatinine (P < 0.01), and total proteins (P < 0.05) were shown in group IV. Treatment with SL400 mg/kg also corrected the increased relative kidney weight in GM-treated animals (P < 0.05). GM nephrotoxicity was shown by elevated levels of malondialdehyde (P < 0.001) and decreased amounts of catalase (P < 0.001), superoxide dismutase (P < 0.01), and glutathione (P < 0.01) in renal tissue. The oxidative injury induced by GM was prevented by SL400 mg/kg treatment. Such treatment also normalized abnormal renal histology induced by GM. These data suggest that treatment with SL extract may be helpful to reduce gentamicin-induced nephrotoxicity. [ABSTRACT FROM AUTHOR]

The aim of this study was to assess changes in the estimated glomerular filtration rate (eGFR) in gouty patients with chronic kidney disease (CKD) using a "treat-to-target" (T2T) approach in gout. This multicenter observational retrospective study included patients diagnosed with gout and CKD stage 3 taking xanthine oxidase inhibitors (XOIs) (allopurinol or febuxostat) for at least 12 months. All patients were treated using a T2T strategy according to national gout guidelines to achieve the target levels of serum uric acid (sUA; < 5–6 mg/dl) within 6 months of the first visit. The primary outcome was to assess changes in eGFR. The effects of independent variables were analyzed over eGFR in a linear mixed-effects (LME) model. Fifty patients with gout and CKD stage 3 treated with XOIs with a T2T strategy for 12 months were included. Eighty-two percent of the patients achieved the sUA target during the study period. The improvement seen in eGFR was higher during the first 6 months, showing a median increase of 7.54 ml/min/m2 (SE = 1.25) and trending towards stability over 12 months. For every 1 mg/dl of decrease in sUA, an improvement of 1.5 ml/min/m2 in eGFR was observed (coefficient ± SE: − 1.58 ± 0.26) (p < 0.001) with no differences between type and dosage of XOIs treatment, colchicine administration, age, sex, and smoking status. A reduction in sUA levels using a T2T approach with XOIs at an optimal dose is possible and could help conserve and improve renal function in gouty patients with CKD stage 3. [ABSTRACT FROM AUTHOR]

Background: There is high incidence of liver and kidney diseases worldwide but medicinal plants may provide remedy. This study evaluated and compared the protective effects of Cassia spectabilis extract (CSE) and Newbouldia laevis extract (NLE) against diclofenac (DF) induced hepatorenal oxidative damage in rats. Methods: Twenty four rats were divided into 4 groups with 6 rats in each. Normal saline was given to the rats in group I while those in groups III and IV were treated with 250 mg/kg b. wt. CSE and NLE respectively for 28 days by oral gavages. Those in groups II to IV were exposed to 10 mg/kg DF in the last 7 days of treatment. Serum was separated from the blood and used for estimations of hepatorenal injury markers while the homogenized tissue supernatants were used for assays of oxidative stress markers. Results: There was a significant (p < 0.01) increase in the levels of ALT, AST, GGT, MDA, creatinine and BUN but a significant (p < 0.01) decrease in the levels of SOD, CAT, GPx, GST, GSH and G6Pase of DF-exposed rats when compared with normal control. However, treatment of DF-exposed rats with CSE and NLE significantly (p < 0.01) increased the levels of SOD, CAT, GPx, GST, GSH, and G6Pase but significantly (p < 0.01) reduced the levels of ALT, AST, GGT, MDA, creatinine and BUN when compared with DF control. Conclusion: The current findings showed that treatments with CSE and NLE may have protective effects against DF-induced hepatorenal oxidative damage in rats, attributed to certain phytochemicals, but CSE has greater bioactivity than NLE. [ABSTRACT FROM AUTHOR]

Chronic kidney disease (CKD) is a global healthcare problem; however until now, there is no effective treatment that can stop its progression. In this study, we aimed to investigate the effect of empagliflozin, a sodium-glucose linked transporter-2 inhibitor (SGLT2I) in a model of unilateral ureteric obstruction (UUO) in rats, as a model of progressive renal interstitial fibrosis in vivo and the possibility of inclusion of klotho protein. Rats were randomly divided into five groups: group 1: control group, group 2: UUO untreated group, group 3: prophylactic SGLT2I treatment before UUO, group 4: immediate SGLT2I treatment after UUO, and group 5: delayed SGLT2I treatment (this group received distilled water 1 week after UUO then empagliflozin for 2 weeks). At the end of the experiment period, animals were sacrificed, and kidney fibrotic and inflammatory parameters were measured. Also kidney sections were examined histopathologically for CTGF expression. UUO resulted in renal dysfunction and fibrosis through upregulating inflammatory cascade (NF-κB-TLR4) as well as many fibrotic pathways (as TGF-β1, αSMA, Wnt, CTGF, and fibronectin) with significant reduction in the klotho protein expression. We hypothesized that both prophylactic and immediate treatment with empagliflozin after UUO in rats exert more renoprotective effect in comparison with delayed treatment via enhancement of renal klotho expression and activity, for further investigations. [ABSTRACT FROM AUTHOR]

Purpose: Drug-induced nephrotoxicity is one of the most common side effects of medications and accounts for about 20 % of hospital admissions for acute kidney injury (AKI). Some possible pharmacologic mechanisms of pentoxifylline (PTX) that suggest it as a candidate to ameliorate AKI include interaction at the level of the adenosine receptors, increase in erythrocyte deformability, stimulation of vasodilatory prostaglandins production and prevention of vascular congestion, and suppression of tumor necrosis factor alpha (TNF-α) and apoptosis. This manuscript reviews all clinical and animal studies on the use of PTX as a renoprotective agent against a number of nephrotoxic drugs. Methods: Data were collected by searching MEDLINE, PubMed, Scopus, Cochrane central register of controlled trials, and Cochrane database systematic reviews. Key words used as search terms were pentoxifylline, nephroprotective, renoprotective, drug-induced renal diseases, drug-induced nephrotoxicity, drug-induced renal toxicity, and drug-induced nephropathy. This search was performed without time limitation. Results and conclusion: Most greatest number of studies and human clinical trials on the renoprotective effect of PTX against drug-induced nephrotoxicity involves cyclosporine (Cyc). It seems that despite encouraging results from animal studies, there is insufficient evidence to support the renoprotective effect of PTX against Cyc-induced nephrotoxicity in humans. Although some available animal studies show protective effects of PTX against renal toxicity of some antimicrobial and cytotoxic agents, designing clinical trials to approve these nephroprotective effects requires prior confirmation of no reducing antimicrobial or antitumor action of these medications by PTX. [ABSTRACT FROM AUTHOR]

Present study reports the effects of metanil yellow, a non-permitted food colouring dye, on the biomarkers of oxidative stress and kidney function in blood and renal tissue of albino Wistar rats and its mitigation by cinnamaldehyde, a major phytoconstituents of cinnamon. Oral administration of metanil yellow in rats caused about 70% reduction in ferric reducing ability (FRAP 5.1 μM/L) and 50% decline in reduced glutathione (GSH 59.27 nM/mg protein) content in plasma with simultaneous increase in serum creatinine level. In kidney tissues, activities of superoxide dismutase (SOD), catalase and GSH dropped while malondialdehyde (MDA) content increased. Co-administration of cinnamaldehyde with metanil yellow showed considerable restorative effect on the biomarkers of plasma antioxidant status and kidney function i.e., FRAP (11.5 μM/L), GSH (83-88.5 nM/mg protein), urea, creatinine, SOD, catalase and MDA. Administration of cinnamaldehyde restored the kidney enzyme activities up to 75% of the base level. The study revealed that reno-protective action of cinnamaldehyde was mediated by lowering oxidative stress level. [ABSTRACT FROM AUTHOR]