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  • Ezatiostat hydrochloride synthesis Curcumin is the principal

    2024-07-10

    Curcumin is the principal natural polyphenol curcuminoid of turmeric (Curcuma longa) rhizome, a member of the ginger family (Zingiberaceae) [13]. Curcumin has a wide spectrum of therapeutic properties, and it has been shown to possess antioxidant, anti-inflammatory, anticancer, antiangiogenesis, chemopreventive, and chemotherapeutic properties [14], [15], [16], [17], [18]. Studies on the effect of curcumin on Ezatiostat hydrochloride synthesis involved in degradation of renal adenosine and l-arginine metal toxicity in animal models are scarce. Therefore, the present study highlighted other significant aspects that underline Cd/curcumin exposure. Hence, we investigated the effect of curcumin on arginase and ADA activities in Cd-induced renal toxicity in rats.
    Materials and methods
    Results
    Discussion At present, therapeutic modalities to prevent or treat acute renal injury related to metal poisoning are extremely limited, and the search for novel therapeutic interventions is an area of intense investigation. Recent studies implicate the endogenous signaling molecule adenosine in kidney function/protection. As such, enzymatic production of adenosine from its precursor molecules ATP and AMP, and regulation of its level by ADA play a critical role in attenuating renal damage and preserving kidney function during episodes of renal metal poisoning [11], [12]. The result of the present study demonstrated that ADA activity was significantly increased in the kidney of Cd-treated rats when compared with the control (p < 0.05) (Figure 1). Previous studies have demonstrated upregulation in the ADA activity in renal injury [29], [30], [31], [32]. The increase in ADA activity found in this study could result in a decrease in the level of adenosine, a renoprotector molecule [11], [12]. Extracellular adenosine primarily functions as a signaling molecule and can signal through four adenosine receptors (ARs): A1AR, A2AAR, A2BAR, and A3AR [33]. Several studies have implicated the levels of adenosine in hypoxia, inflammation, or acute renal injury [11], [34], [35]. It is interesting to note that co-treatment with curcumin was able to prevent an increase in ADA activity in Cd-intoxicated rats (Figure 1). This suggests that curcumin has a protective role against Cd poisoning, and the probable mechanism could be due to their inhibitory effect on renal ADA activity, thereby resulting in an increase in the level of adenosine. Previous studies have implicated curcumin and adenosine levels via modulation of the purinergic system in various pathological conditions such as Alzheimer's disease, diabetes, stroke, hypertension, and inflammation [21], [36]. Arginase enzyme has been implicated to play a significant role in kidney function. This study shows that pharmacological inhibition of renal arginase activity (Figure 2) in curcumin-treated rats mediates renal tissue protection, as proved by a reduction in serum urea, creatinine, and electrolyte levels (Table 1) during Cd poisoning. These findings further reveal an important role of arginase activity in the pathogenesis of renal injury and provide evidence for arginase inhibition as a potential therapeutic modality for treating metal poisoning. An elevated arginase activity has been linked to several vascular problems including hypertension, atherosclerosis, and end-stage kidney damage [37], [38], [39]. Previously, we showed activation of arginase as a key mediator of kidney injury (Figure 2). Enhanced arginase activity can impair endothelium-dependent vasorelaxation by decreasing L-arginine availability to eNOS, thereby reducing NO production and uncoupling eNOS function [9]. We observed a significant decrease in the level of NO in Cd-induced renal damage (Figure 3). The result is in agreement with Figure 2, where we observed an increase in arginase activity that can deplete NO production. However, treatment with curcumin, the principal active ingredient in turmeric, restores the level of NO in Cd-intoxicated rats. This increase in NO could be a result of the fact that curcumin exhibited an inhibitory effect on arginase activity [40]. There is increasing evidence that NO, a potent vasodilator, is one of the most important paracrine modulators and mediators in the control of renal functions, such as overall and regional renal blood flow, renal autoregulation, glomerular filtration, renin secretion, and salt excretion [41], [42]. NO also plays an important role in the pathogenesis of several renal disease states, such as diabetic nephropathy, inflammatory glomerular disease, acute renal failure, and nephrotoxicity of drugs/metals, conveying both beneficial effects via its hemodynamic functions [41], [42].