Cadmium is a widespread environmental xenobiotic that poses serious risks to hepatic, renal, and male reproductive functions. Natural compounds such as silymarin, a bioactive extract from Silybum marianum, have gained attention for their protective potential against xenobiotic-induced toxicity. This study investigated whether subchronic oral administration of silymarin (30 mg/kg) mitigates cadmium-induced toxicity (5 mg/kg) in adult rats over six weeks. Twenty-four rats were assigned to four groups: control, cadmium-exposed, silymarin-treated, and co-treated. Biochemical, hematological, oxidative stress, and reproductive parameters were assessed. Sperm quality was evaluated using CASA, and testicular tissues were examined histologically. Cadmium exposure significantly reduced body weight (−30.8%), elevated transaminases (AST, ALT; p < 0.01), increased serum creatinine and total cholesterol, and induced multi-organ oxidative stress, as reflected by elevated malondialdehyde and markedly reduced SOD, CAT, and thiol group levels in testicular, hepatic, and renal tissues (p < 0.01). Sperm concentration dropped from 75.2 to 21.8 × 10⁶/mL, with total motility falling to 35% and progressive motility to 18%, accompanied by severe seminiferous tubule degeneration (Score III in 5 rats). Co-administration of silymarin partially restored these parameters, sperm concentration recovered to 38.5 × 10⁶/mL, total motility improved to 50.2%, and antioxidant enzyme activities and liver/kidney biomarkers showed significant but incomplete recovery (p < 0.05). Molecular docking revealed favorable binding affinities of silybin toward GPx (−8.4 kcal/mol), CAT (−8.3 kcal/mol), and SOD (−6.4 kcal/mol), offering a preliminary computational hypothesis suggesting possible interactions between silybin and antioxidant enzymes, pending experimental validation. Silymarin alone exerted no adverse effects. These findings establish silymarin as a partial but promising multi-organ cytoprotectant against cadmium toxicity, and highlight the need for future studies optimizing dosing strategies, exploring longer treatment durations, and investigating combination approaches with metal chelators or Nrf2-activating agents to achieve complete tissue recovery.

Background: Obesity, primarily driven by high-calorie and high-fat diets, is a major public health issue and a key risk factor for kidney dysfunction. It triggers glomerular hyperfiltration and oxidative stress, which can lead to chronic kidney disease (CKD). Spirulina has emerged as a potent natural agent with strong antioxidant and anti-inflammatory properties. Objectives: This study was conducted to evaluate the protective effects of spirulina (SP) against cafeteria diet (CD)-induced renal tissue alterations and oxidative stress in obese rats. Methods: Rats were divided into four groups and treated daily for eight weeks: the control group (standard diet (SD) 360 g/d), a cafeteria diet group (CD 360 g/d), a spirulina group (SP 500 mg/kg body weight (b.w.) administered orally (p.o.)), and a CD + SP group (500 mg/kg b.w., p.o.) We also performed an in silico molecular docking study with spirulina’s bioactive compound, phycocyanobilin. Results: Our findings showed that CD feeding led to an increase in body weight, kidney weight, and abdominal fat. In addition, severe renal alterations and disturbances in serum metabolic parameters associated with oxidative stress were observed in response to CD-induced obesity. However, SP administration significantly reduced body weight and total abdominal fat and improved lipid profiles. SP supplementation also notably improved oxidative status and protected against histological injury and disturbances. The in silico analysis predicted a favorable binding affinity of the phycocyanobilin compound for human CAT and GPx and a moderate predicted affinity for TNF-α and IL-6; these predictions are hypothesis-generating, as no direct target-engagement assays were performed. Conclusions: Taken together, these findings demonstrate the beneficial effects of SP on obesity induced by a cafeteria diet (CD), suggesting its potential in protecting against disturbances in renal function associated with oxidative stress and histological alterations.