Introduction: Cysteamine, a powerful endogenous antioxidant, is produced mostly by the vanin-1 with pantetheinase activity. With regard to glycemic, inflammatory, and redox factors, the current study sought to evaluate the association between the expression of the vanin-1 gene, oxidative stress, and inflammatory and iNOS signaling pathway in obese diabetic patients. Methods: We enrolled 67 male subjects with an average age of 53.5 ± 5.0 years, divided into 4 groups according to the WHO guideline. We determined their plasma levels of glucose, insulin, IRI, HbA1c, TC, TG, HDL-C, TNF- α, MCP-1, TGF-β 1, SOD, CAT, and TBARs, as well as expression of the iNOS and Vanin1 genes. Results: Overweight and obese class I and II diabetics had significantly higher levels of plasma glucose, insulin, HbA1c, TNF-α, MCP-1, TGF-β 1, CAT, and TBAR as well as iNOS and vanin-1 gene expression compared to healthy control individuals. In addition, as compared to healthy control individuals, overweight obese class I and II diabetics’ plasma HDL-C levels and blood SOD activity were significantly lower. In addition, ultrasound and computed tomography showed that the presence of a mild obscuring fatty liver with mild hepatic echogenicity appeared in overweight, class I and II obese diabetic patients. Conclusion: These findings provide important information for understanding the correlation between Vanin 1 and glycemic, inflammatory, and redox factors in obese patients. Furthermore, US and CT analysis were performed to visualize the observed images of fatty liver due to obesity. Graphical Abstract:

The possible impact of topiramate against diabetic retinopathy (DREN) and its molecular mechanisms in relation to the nod-like receptor family pyrin domain containing 3 (NLRP3) inflammasome has not been studied before. Thus, in the present study, we aimed to utilize a computational approach to investigate the possible protective effect of topiramate on experimental DREN and explore its impact on NLRP3/interlukin-1β signaling and brain-derived neurotrophic factor (BDNF) expression. Male albino mice were distributed to four experimental groups and assigned the following categorizations: (i) saline, (ii) diabetic, (iii) diabetic + topiramate 10 mg/kg and (iv) diabetic + topiramate 30 mg/kg. We observed shrinkage of total retinal thickness and elevation in retinal glutamate, malondialdehyde, NLRP3 and interlukin-1β but decreased glutathione (GSH) levels in the diabetic mice. Additionally, retinal ultra-structures in the diabetic group showed abnormalities and vacuolations in the pigmented epithelium, the photoreceptor segment, the outer nuclear layer, the inner nuclear layer and the ganglion cell layer (GCL). Mice treated with topiramate 10 or 30 mg/kg showed downregulation in retinal malondialdehyde, NLRP3 and interlukin-1β levels; improvements in the retinal pathologies; enhanced immunostaining for BDNF and improved ultra-structures in different retinal layers. Overall, the current results suggest topiramate as a neuroprotective agent for DREN, and future studies are warranted to further elucidate the mechanism of its protective action.

Chronic kidney disorder is a rising danger to health that affects a significant percentage of older adults, and a crucial stage in its development is fibrosis. MicroRNAs and transforming_ growth factor-β1(TGF-β1) /SMAD2 signal pathway significantly regulate this process. miR-34a promotes extracellular matrix (ECM) deposition and inhibits B cell lymphoma-2 (Bcl-2), a target gene with antifibrotic properties shown to protect against renal fibrosis in animal models. Currently, several drugs, including entacapone, have been reported to suppress miR-34a activation. Experimental model of Carbon- tetrachloride (CCl₄)-induced renal fibrosis revealed elevated serum levels of urea and creatinine, an increased urinary microalbumin-to-creatinine ratio, deterioration of the antioxidant-oxidant balance, an increase in TGF-β1 in renal tissue, and increased renal miR–34a–SMAD2 expression were observed, accompanied by decreased expression of Bcl-2. Entacapone holds reno-protective promises likely via its anti-inflammatory-antioxidant effects in CCl₄-induced renal fibrosis by favorable modulation of miR-34a /TGF-β1/SMAD2 Signaling Pathway.

Background: Despite the frequent inclusion of fluid therapy in the treatment of many conditions, there are limited studies available to provide an evidence-based specific recommendation for fluid therapy in acute drug toxicity. Salicylate toxicity is considered one of the common clinical problems. It is commonly associated with fatal complications and even can lead to death. The study was designed to investigate the effects of various IV fluid types as isotonic saline (NaCl 0.9%), Ringer lactate (RL), and albumin and their impact on acetyl salicylic acid (ASA) toxicity outcome in a rat model of acute salicylate toxicity. Sixty male Albino rats were divided into 10 groups of 6 rats each. The first four groups were the control, saline, RL, and albumin groups. The fifth group received two doses of ASA solution orally, and the next five groups were treated with IV fluids as follows: saline-ASA, RL-ASA, albumin-ASA, RL + albumin-ASA, and saline + albumin-ASA. Upon completion of the study, spirometry, arterial blood gas analysis (ABG), and serum liver and kidney function tests were done on all groups. Furthermore, quantitative real-time polymerase chain reaction (PCR) was used to assess interleukin-6 (IL6), nuclear factor kappa beta (NF-kβ), and beta-actin mRNA gene expression of histopathology and immunohistochemistry assessments were also performed on liver and kidney tissues. Results: The results revealed the ASA group showed marked deterioration across all the investigated parameters. The groups that received saline and RL showed improvements in the following: respiratory rates, ABG, liver and kidney function, and histopathological findings. The RL + albumin group did not show any improvements. The albumin group and the saline + albumin group showed variable responses, ranging from mild improvement to no improvement. Conclusions: The saline and RL groups showed positive results; however, the RL + albumin group showed the worst outcomes. The inclusion of albumin did not appear to provide any extra benefits and produced varying results.

Background: Streptozotocin (STZ) is a glucose analogue commonly used for inducing diabetes in experimental animals. This study is intended to investigate the ability of captopril (Cap) pretreatment to augment STZ-induced diabetogenic effect in an experimental rat model. If this hypothesis were proven, Cap administration to rats could reduce the dosage of STZ by augmenting its effect and resulting in a subsequent reduction in STZ cost. Forty-two adult male Wistar rats were randomly divided into seven groups: a control group that fed a normal diet, whereas the other six experimental groups were fed a high-fat diet (HFD). The six groups were then divided into STZ-30, STZ-30-Cap, STZ-40, STZ-40-Cap, STZ-50, and STZ-50-Cap. All Cap-received groups were supplemented with 50 mg/kg Cap orally one hour just before intraperitoneal (I.P.) injection of STZ. 30-STZ, 40-STZ, and 50-STZ-treated groups were injected once with STZ I.P. at doses of 30, 40, and 50 mg/kg, respectively. An intraperitoneal glucose tolerance test (IPGTT) was done. Pancreatic tissue was obtained to measure Tumor necrosis factor alpha (TNF-α), interleukin one beta (IL-1β), and nitric oxide (NO) by enzyme-linked immunosorbent assay (ELISA) and glucose transporter 2 (GLUT2) gene expression by reverse transcription polymerase chain reaction (RT-PCR). Pancreatic sections were examined by hematoxylin and eosin (H&E) stain, and immunohistochemical staining by anti-insulin and anti-TNF-α antibodies. Results: Results indicated that administration of Cap before STZ in different doses significantly augmented the hyperglycemic state that was evident by intraperitoneal glucose tolerance test, and markedly increased pancreatic pro-inflammatory markers. Histological analysis of islets of Langerhans indicated degeneration with extensive vacuolations associated with a significant decrease in mean area % of insulin immunoreactivity and an increase in optical density of TNF-α immunoreactivity. Conclusion: These findings pointed to the ability of captopril pretreatment to augment the hyperglycemic state and the diabetogenic response that was induced secondary to STZ injection in an experimental rat model.

Globally, hepatocellular carcinoma (HCC) presents a clinical and financial burden, as it is often diagnosed at a later stage. Cisplatin is one of the most commonly used chemotherapeutics for treating various types of solid tumours; however, it is a double-edged sword due to its cytotoxic effects. Consequently, we hypothesized that combining cisplatin with melatonin could be effective in treating HCC. Additionally, melatonin may mitigate the severe adverse effects of cisplatin on normal cells through its cellular protection, immunomodulation, and antioxidant activities. Forty male adult Wistar rats were randomly divided into five groups: Group 1(n = 8), negative control group. HCC was induced in 32 rats with diethyl nitrosamine and carbon tetrachloride injection. Following induction, rats were divided into group 2 (HCC): diseased control; group 3 (HCC-Cis): HCC rats received cisplatin (2.5 mg/kg I.P. once every week for 3 weeks); group 4 (HCC-Melatonin): HCC rats received melatonin in drinking water (20 mg/L for 3 weeks); and group 5 (HCC-Cis-Melatonin; Combined therapy): the HCC rats received both cisplatin and melatonin. HCC group revealed significant elevation in ALT, AST, and AFP associated with increased TNF-α and MDA levels. Hepatic tissue exhibited a significant increase in VEGF, MDM2, COX-2, and miR-155, and a decrease in caspase-3 associated with hepatic damage, ballooning of hepatocytes, and increased BCL-2 and CD68 immunostaining. Although cisplatin was able to induce HCC apoptosis by COX-2 and MDM2/p53/ miR-155 modulation, it aggravated normal hepatocytic damage that was improved by the antioxidant and anti-inflammatory effects of melatonin. In conclusion, melatonin and cisplatin co-administration may be a viable strategy to preserve liver function by shielding healthy hepatocytes from the cytotoxic effects of cisplatin.