# Litholytic Activities of Natural Bioactive Compounds and Their Mechanism Insights
## 5 Litholytic Activity of Other Compounds
### In Vivo Investigations
In animals treated with EG (hyperoxaluric rats), selenium at 10 mg/100 g decreased the reabsorption of the magnesium fraction, the ionic product (4.03 vs. 6.72 mg/g), and the oxalate and calcium concentrations (0.81 vs. 1 mg/g and 4.98 vs. 6.11, respectively) [54]. In contrast, no effect on urinary excretion, urinary urea excretion, Ca/Mg ratio, GFR, and fractional reabsorption of water and phosphate compared to the control group was reported. [PERSON] et al. [60] investigated, in vivo, the antilithiasic effect of rotterlin (from the fruits of _Mallotus philipensis_ (Lam.)) at 1 mg/kg/day on CaOX induced by the administration of 0.4% EG and 1% ammonium chloride. At 1 mg/kg/day, rotterlin enhanced the activities of antioxidant enzymes (CAT and SOD) and refurbished MDA levels and the redox ratio in hyperoxaluric rats. Additionally, rotterlin maintained creatinine clearance (2.43 vs. 2.84 mL/min) and urinary excretion of calcium and oxalate (3.35 vs. 2.88 mg/dL and 1.13 vs. 0.92 mg/day, respectively) compared to normal rats [60], whereas no significant change in the level of alkaline phosphatase in the serum has been reported. Furthermore, rotterlin significantly decreased the activity of LDH and lipid peroxidation in nephrolithiasis rats (41.28 vs. 49.74 IU/L and 5 vs. 10 nmol of MDA formed/mg protein, respectively). The authors confirmed that rotterlin decreased the translocation of protein kinase C \(\delta\) (PKC) from the cytoplasmic fraction to the membrane and the mitochondrial fraction, suggesting an inhibition of PKC\(\delta\) activity as well as a reduction in NADPH oxidase activity [60]. These findings suggest further studies to determine the mechanisms by which these compounds exactly act. Moreover, clinical investigations of these compounds were also suggested in many different studies. The antiurolithiasis effect of taraxasterol at different concentrations (2, 4, and 8 mg/kg) on EG-induced urolithiasis rats was evaluated by [PERSON] et al. [49]. At 2 mg/kg, taraxasterol exhibited a potent and very significant decrease in hepatic and renal coefficients in vivo (0.029 vs. 0.042 and 0.004 vs. 0.008, respectively). Serum analysis revealed a significant decrease in calcium, ALT, AST, and LDH levels compared to lithiasis rats (12.5 vs. 13.5 mg/dL, 43.9 vs. 52.2 UI/L, 44.8 vs. 49.5 UI/L, and 1105 vs. 1318 UI/L, respectively), while serum albumin, magnesium, SOD, and GPx levels increased (3.6 vs. 3 mg/dL, 0.86 vs. 0.78 mg/dL, 90 vs. 81 UI/L, and 226 vs. 210 UI/L, respectively) [49]. In parallel, taraxasterol significantly reduced the score of crystal deposits, pathological damage, and inflammation compared to lithiasis rats (3.5 vs. 5.5, 2 vs. 5.3, and 0 vs. 2.5, respectively). These authors suggest that taraxasterol interacts with CaOx crystals, promotes oxidative enzymes (SOD and GPx), and reduces inflammatory cytokines such as TNF-\(\alpha\), IL-6, and IL-1\(\beta\), which reduce the production of ROS. Recently, [PERSON] et al. [46] evaluated in vivo the effect of DADS and DATS at different concentrations (8 and 15 mg/kg) on urolithiasis induced by EG and ammonium chloride in rats. DADS and DATS significantly increased Cx43 and SOD1 expression levels in the model group compared to expression levels in the control group. Furthermore, allicin significantly decreased renal crystal deposition in rats and increased Cx43 expression in kidney. From this research, the authors suggested that DADS and DATS modulate GJs, Cxs, inflammation, and oxidative stress, which prevent nephrolithiasis [46].