Gum Arabic (GA) extract, rich in polyphenols and phenolic acids, has shown promising effects in various biomedical applications. Acute renal injury (AKI) is a serious condition with high morbidity and mortality, while heat stress can exacerbate kidney damage. This study aimed to assess the antioxidant, anticancer, antimicrobial, and antidiabetic activities of GA extract, and to evaluate its protective role against heat stress and cisplatin-induced AKI in rats. A total of 210 mice were divided into seven groups (n=10 each), with three replicates: control, AKI, heat stress, low-dose GA (2%), high-dose of GA (10%), Cisplatin+high-dose of GA, and heat stress+high-dose of GA. Heat stress proteins (HSP70, HSP90), renal function markers (urea, creatinine), lipid profile (TC, TG, LDL, HDL) glucose and insulin level, sex hormones (testosterone, LH, FSH), oxidative stress parameters (MDA, CAT, SOD, GPx), inflammatory markers (TNF-α, IL-1β), and precancerous markers (BAX, Casp-3)  were measured. The results indicated that GA extract demonstrated significant antioxidant, anticancer, antimicrobial, and antidiabetic activities, where scavenged 92% of DPPH free radicals, reduced 85% of breast cancer cell lines, and inhibited the growth of pathogenic bacteria and fungi in the MIC range of 0.5-2%. Furthermore, it inhibited the α-amylase and α-glucosidase by 78 and 85%, respectively. GA also ameliorated renal function markers and reduced oxidative stress by decreasing MDA, glucose, and insulin levels, while increasing CAT, SOD, GPx, and reproductive hormones levels. It downregulated pro-inflammatory cytokines and precancerous markers, increased HSP70 and HSP90 levels, and mitigated histopathological alterations in the kidneys of AKI rats. These findings suggest that the antioxidant and anti-inflammatory properties of GA contribute to its renoprotective effects. Thus, GA extract may offer a promising natural therapeutic approach for mitigating heat stress and managing cisplatin-induced AKI.

To Cite This Article: Alharthi NS, Salah KBH,‏ Al-Zahrani MH, Alyoubi AA, Abu-Zinadah GMA, Alhazmi WA, Momenah MA, Alqahtani MA, Mashraqi A and Sadan M, 2025. Polyphenolic Gum Arabic Extract with Antidiabetic, Antioxidant, Anticancer, and Antimicrobial Activities Enhances Blood Biochemistry, Heat Stress Genes, and Reproductive Hormones in Heat and Cisplatin Nephrotoxicity-Stressed Mice. Pak Vet J. http://dx.doi.org/10.29261/pakvetj/2025.121