Tilmicosin (Til) is a popular macrolide antibiotic, widely used in veterinary practice. The present study was designed to address the efficacy of Moringa oleifera ethanolic extract (MOE) in protecting against Tilmicosin (Til) - induced nephrotoxicity in Sprague Dawley rats. Animals were treated once with Til (75 mg/kg bw, subcutaneously), and/or MOE for 7 days (400 or 800 mg/kg bw, by oral gavage). Til-treatment was associated with significantly increased serum levels of creatinine, urea, sodium, potassium and GGT activity, as well as decreased total protein and albumin concentrations. Renal tissue hydrogen peroxide (H₂O₂) and malondialdehyde (MDA) levels were elevated, while the activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx) enzymes were diminished. The levels of renal tumor necrosis factor alpha (TNF-α) and interleukin-1 beta (IL-1β) and the mRNA expression of intermediate filament protein encoding genes (desmin, nestin and vimentin) in the kidney were up- regulated with histopathological alterations in renal glomeruli, tubules and interstitial tissue. These toxic effects were markedly ameliorated by co-treatment of MOE with Til, in a dose dependent manner. Taken together, these results indicate that MO at 800 mg/kg protects against Til-induced renal injury, likely by its potent antioxidant and anti-inflammatory properties, which make it suitable to be used as a protective supplement with Til therapy.

Gibberellic acid (GA3), a widely known plant growth regulator, has been mostly used in agriculture. Little is known regarding its toxicity or the impact of its metabolic mechanism on human health. The current study examined the protective impact of chrysin against GA3-induced liver and kidney dysfunctions at biochemical, molecular, and histopathological levels. Forty male albino rats were allocated into 4 groups. The control group received saline; the chrysin group received 50 mg/kg/BW orally daily for 4 weeks; the GA3 group received 55 mg/kg/BW GA3 via daily oral gavage for 4 weeks, and the protective group (chrysin + GA3) was administered both chrysin and GA3 at the same dosage given in chrysin and GA3 groups. Chrysin was administered 1 h earlier than GA3. The GA3 induced liver and kidney injuries as proven by the elevation of hepatic and renal markers with a significant increase in malondialdehyde levels. Furthermore, a decrease of catalase and glutathione was reported in the GA3-administered rats. Pre-administration of chrysin significantly protected the hepatorenal tissue against the deleterious effects of GA3. Chrysin restored the hepatorenal functions and their antioxidant ability to normal levels. Moreover, chrysin modulated the hepatorenal toxic effects of GA3 at the molecular level via the upregulation of the antiapoptotic genes, interleukin-10 (IL-10), hemoxygenase-1, and nuclear factor erythroid 2-related factor 2 expressions; the downregulation of the kidney injury molecule-1 and caspase-3 mRNA expressions; and a decrease in IL-1β and tumor necrosis factor-α secretions. Additionally, the pre-administration of chrysin effectively attenuated the GA3-induced hepatorenal histopathological changes by regulating the immunoexpression of cytochrome P450 2E1 (CYP2E1) and pregnane X receptor, resulting in normal values at the cellular level. In conclusion, chrysin attenuated GA3-induced oxidative hepatorenal injury by inhibiting free-radical production and cytokine expression as well as by modulating the antioxidant, apoptotic, and antiapoptotic activities. Chrysin is a potent hepatorenal protective agent to antagonize oxidative stress induced by GA3.

This study examined the effect of sodium salicylates (SS), alone and in combination with curcumin (CUR), on kidney function and architecture in rats. Five rat groups were given 1 mL physiological saline/rat orally, 1 mL olive oil/rat orally, 50 mg CUR/kg bwt orally, 300 mg SS/kg bwt intraperitoneally, or CUR+SS for 15 days. The hematological indices, serum protein profile, serum electrolytes balance, oxidative stress, and lipid peroxidation of kidney tissues were assessed. The histopathological examination and immune expression of Caspase-3 and nuclear factor kappa (NF-κB) were conducted. The findings showed that SS injection induced nephrotoxic activity, including increased serum urea, creatinine, and uric acid levels. It also caused apparent pathological alterations with increased Caspase-3 and NF-κB immuno-expression. In addition, thrombocytopenia, leukocytosis, neutrophilia, hyponatremia, hypochloremia, hypocalcemia, and hypomagnesemia but not hyperkalemia and hyperphosphatemia were evident in SS-injected rats. Moreover, SS exposure increased serum α1 globulin, renal tissue malondialdehyde, and Caspase-3 levels but superoxide dismutase, glutathione peroxidase, and Bcl-2 levels declined. Meanwhile, CUR significantly counteracted the SS harmful impacts on kidneys but SS+CUR co-administration induced an anemic condition. Overall, CUR has an evident protective role against SS-induced renal damage, but the disturbed hematological alterations should be carefully taken into consideration in their combined use.

Objective(s): Reactive oxygen species (ROS)-produced oxidative disorders were involved at the pathophysiology of many inflammatory processes via the generation of pro-inflammatory cytokines and antioxidant defense system suppression. Although herbal antioxidants as mono-therapy relief many inflammatory diseases including, autoimmunity rheumatoid arthritis, but as combination therapy with other proven anti-inflammatory drugs in order to decreasing their toxic impacts has not yet been studied clearly, especially against chemical substances that’s induced local inflammation with characteristic edema. Materials and Methods: Grape seeds extract (GSE) at a concentration of 40 mg/kg B. wt alone or in combination with indomethacin (Indo.) at a dose of 5 mg/Kg B. wt orally given for 10 days prior (gps VI, VII, VIII) or as a single dose after edema induction (gps IX, X, XI) in rat's left hind paw by sub-planter single injection of 0.1 carrageenan: saline solution (1%) (gp. V) to assess the prophylactic and therapeutic anti-inflammatory activities of both through the estimation of selective inflammatory mediators and oxidative damage-related biomarkers as well as tissue mast cell scoring. Furthermore, both substances were given alone (gps II, III, IV) for their blood, liver and kidney safety evaluation comparing with negative control rats (gp. I) which kept without medication. Results: A marked reduction on the inflammatory mediators, edema volume and oxidative byproducts in edema bearing rats' prophylactic and treated with grape seeds extract and indomethacin was observed. Indomethacin found to induce some toxicological impacts which minimized when administered together with GSE. Conclusion: GSE is a safe antioxidant agent with anti-inflammatory property.