Human colon microbiota produce a metabolite called urolithin A (URO A) from ellagic acid and linked compounds, and this metabolite has been demonstrated to have antioxidant, anti-inflammatory, and antiapoptotic activities. The current work examines the various mechanisms through which URO A protects against doxorubicin (DOX)-induced liver injury in Wistar rats. In this experiment, Wistar rats were administered DOX intraperitoneally (20 mg kg⁻¹) on day 7 while given URO A intraperitoneally (2.5 or 5 mg kg⁻¹ d⁻¹) for 14 days. The serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and gamma glutamyl transferase (GGT) were measured. Hematoxylin and eosin (HE) staining was used to evaluate histopathological characteristics, and then antioxidant and anti-inflammatory properties were evaluated in tissue and serum, respectively. We also looked at how active caspase 3 and cytochrome c oxidase were in the liver. The findings demonstrated that supplementary URO A therapy clearly mitigated DOX-induced liver damage. The antioxidant enzymes SOD and CAT were elevated in the liver, and the levels of inflammatory cytokines, such as TNF-α, NF-kB, and IL-6, in the tissue were significantly attenuated, all of which complemented the beneficial effects of URO A in DOX-induced liver injury. In addition, URO A was able to alter the expression of caspase 3 and cytochrome c oxidase in the livers of rats that were subjected to DOX stress. These results showed that URO A reduced DOX-induced liver injury by reducing oxidative stress, inflammation, and apoptosis.

Epilepsy is one of the most common chronic neurodisorders in the pediatric age group. Despite the availability of over 20 anti-seizure medications (ASMs) on the market, drug-resistant epilepsy still affects one-third of individuals. Consequently, this research aimed to investigate the association between single-nucleotide polymorphisms (SNPs) of the ATP-binding cassette subfamily B member 1 (ABCB1) gene in epileptic pediatric patients and their response to ASMs. This multicentric, cross-sectional study was conducted among Saudi children with epilepsy in Jeddah, Saudi Arabia. The polymorphism variants of ABCB1 rs1128503 at exon 12, rs2032582 at exon 21, and rs1045642 at exon 26 were genotyped using the Sanger sequencing technique. The study included 85 children with epilepsy: 43 patients demonstrated a good response to ASMs, while 42 patients exhibited a poor response. The results revealed that good responders were significantly more likely to have the TT genotypes at rs1045642 and rs2032582 SNPs compared to poor responders. Additionally, haplotype analysis showed that the T-G-C haplotype at rs1128503, rs2032582, and rs1045642 was only present in poor responders. In conclusion, this study represents the first pharmacogenetic investigation of the ABCB1 gene in Saudi epileptic pediatric patients and demonstrates a significant association between rs1045642 and rs2032582 variants and patient responsiveness. Despite the small sample size, the results underscore the importance of personalized treatment for epileptic patients.

Objective: To assess the nephroprotective potential of agmatine in a rat model of streptozotocin-induced diabetic nephropathy. Methods: A single dose of streptozotocin (40 mg/kg) coupled with a fructose diet induced diabetes in Wistar rats. Agmatine (40 and 80 mg/kg) was administered to rats for 12 weeks. The body weight and fasting blood glucose were measured weekly. Insulin level, urine output, total protein, albumin, blood urea nitrogen, creatinine, and cystatin-C were also determined at the end of the experiment. Furthermore, superoxide dismutase, glutathione, interleukin-1β, interleukin-6, and tumor necrosis factor-alpha were evaluated in kidney tissue. Histopathological study was also performed using hematoxylin and eosin staining. Results: Agmatine at both doses significantly increased final body weight, and lowered fasting blood glucose, urine output, insulin, total protein, albumin, blood urea nitrogen, creatinine, and cystatin-C levels compared with the diabetic group (P < 0.05). Inflammatory markers and antioxidant effect were significantly improved in agmatine-treated rats. Moreover, the histopathological changes in renal structure were ameliorated by agmatine treatment. Conclusions: Agmatine alleviates diabetic nephropathy by improving renal functions and reducing inflammation and oxidative stress. The molecular mechanisms of its nephroprotective actions need to be investigated in future study.

Background: Methotrexate (MTX) remains the most commonly prescribed drug used to treat rheumatoid arthritis (RA). Polymorphisms in solute carrier organic anion transporter family member 1B3 (SLCO1B3) and SLCO1B1 may play a critical role in MTX pharmacokinetics and patient outcomes. However, research on these polymorphisms in Saudi Arabia remains limited. We evaluated the association of SLCO1B3 (rs4149117, rs7311358) and SLCO1B1 (rs2306283, rs4149056) polymorphisms with MTX efficacy and safety in Saudi patients with RA. Methods: This multicenter, case-control study included patients diagnosed with RA in Jeddah and Taif. Demographic and clinical data were collected and analyzed. Genotyping of SLCO1B3 (rs4149117, rs7311358) and SLCO1B1 (rs2306283, rs4149056) polymorphisms was performed using Sanger sequencing. Statistical analyses, including logistic regression and haplotype analysis, were conducted to evaluate associations between these polymorphisms, MTX efficacy, and toxicity. Results: The study cohort comprised 100 patients with RA, with 46 showing a good response to MTX and 54 showing a poor response. Clinical predictors of MTX response were significantly higher in patients with poor response. Both SLCO1B3 polymorphisms (rs4149117, rs7311358) were significantly associated with anemia. Significant associations were found between SLCO1B1 (rs2306283) and gastrointestinal disturbances and anemia. The GAAT haplotype was significantly more prevalent among good responders, while the TGGT haplotype was significantly associated with poor responders. Conclusions: These results highlight the importance of genetic testing in predicting MTX treatment outcomes and tailoring personalized treatment plans for patients with RA to improve efficacy and minimize adverse effects.

Background and Objectives: Epilepsy is a chronic brain disease, with inherent and noninherent factors. Although over 20 anti-seizure medications (ASMs) are commercially available, nearly one-third of patients develop drug-resistant epilepsy. We evaluated the association between the clinical features and the methyl tetrahydrofolate (MTHFR) rs1801133 polymorphism and ASMs response among pediatric patients with epilepsy. Materials and Methods: This was a multicenter, retrospective, case–control study of 101 children with epilepsy and 59 healthy children in Jeddah. The MTHFR rs1801133 polymorphism was genotyped using the real-time polymerase chain reaction TaqMan Genotyping Assay. Results: Among the patients with epilepsy, 56 and 45 showed good and poor responses to ASMs, respectively. No significant genetic association was noted between the single-nucleotide polymorphism (SNP) rs1801133 within the MTHFR gene and the response to ASMs. However, a significant association was noted between reports of drug-induced toxicity and an increase in allele A frequencies. The MTHFR rs1801133 genotype was significantly associated with the development of electrolyte disturbance among good and poor responders to ASMs. Conclusions: This is the first pharmacogenetic study of MTHFR in patients with epilepsy in Saudi Arabia that found no significant association between the MTHFR SNP rs1801133 and gene susceptibility and drug responsiveness. A larger sample size is needed for testing gene polymorphisms in the future.

Background/Objectives: Methotrexate (MTX) is currently the most widely used treatment for Rheumatoid Arthritis (RA) due to its demonstrated efficacy and well-known safety profile. However, the effectiveness and toxicity of MTX can vary among patients, partly due to genetic factors. Therefore, this study aimed to investigate the associations between the polymorphisms in the ABC subfamily G member 2 (ABCG2) gene and MTX effectiveness/toxicity in Saudi Arabia RA patients. Methods: The study is a retrospective, multicenter, case–control study that uses Sanger sequencing techniques for genotyping. Results: More than half of the patients (55.56%) were poor responders, with a slightly higher mean age. However, there was no significant difference between the two groups, not only in terms of age but also in other demographics and clinical factors. Regarding the rs2231137 polymorphism, the CC, CT, and TT genotype frequency were 91%, 7%, and 2%, respectively. The mutated variant (TT) was only observed in the positive rheumatoid factor group. Notably, none of these genotypes displayed any significant correlation with demographic characteristics, clinical features, or MTX efficacy/toxicity. Conclusions: This study is the first pharmacogenetic study of rs2231137 polymorphism in RA patients utilizing linear regression, revealing that rs2231137 polymorphism is not a predictor of either MTX efficacy or toxicity in RA patients. Therefore, more research is needed.