**7. Counteracting Effects of Natural Products, Chemicals and Pharmacological Agents on Cadmium-Induced Kidney Injury**

In further support of the notion that oxidative stress and oxidative damage are the universal mechanisms underlying renal toxicity by cadmium, we herein tabulate evidence that numerous natural products such as plant extracts and herbal medicines have been used to counteract the oxidative, deleterious effects of cadmium on the kidney. Many of these studies used cadmium-induced animal models of kidney injury as a platform [120]. Table 1 selectively shows some of the reported plant extracts and herbs as well as exogenous chemicals and pharmacological agents that can attenuate cadmium-induced oxidative stress involved in kidney injury. Additionally, many of these approaches can also induce the activation of endogenous cellular defense systems such as Nrf2, superoxide dismutase, glutathione peroxidase, and catalase [74,121–124]. Some studies using kidney cell lines such as HEK293 are also included in the table. It should be pointed out that among all the compounds and chemicals listed in Table 1, it is very difficult to identify which one would be the most efficient in terms of combating confirmed cadmium-induced kidney injury as cross examination and comparison of these natural products on a same platform under exactly the same experimental conditions have not been conducted. In addition, whether administration of these natural antioxidants could increase the efflux of cadmium out of the body remains to be investigated.

**Table 1.** Counteracting effects of exogenous compounds such as plant extracts, herbs, chemicals and pharmacological agents on cadmium induced renal toxicity.



**Table 1.** *Cont.*

\*\* Please note that licorice could also pose renal toxicity under certain conditions [186].

#### **8. Other Potential Interventional Approaches**

In addition to the plant extracts, herbs and pharmacological agents as shown in Table 1, there are other approaches that have also been applied to counteract cadmium-induced kidney injury. For example, caloric restriction as an established interventional approach for aging and age-related diseases [187–190] has been demonstrated to mitigate cadmiuminduced renal toxicity and kidney dysfunction [191]. Dietary restriction of calcium intake has also been shown to enhance cadmium-induced expression of metallothionein, which could minimize cadmium toxicity [192]. The protective effects of preconditioning and postconditioning observed in numerous studies [193–195], if any, elicited by a variety of approaches including ischemia, hypoxia, chemicals or pharmacological agents are yet to be investigated. Additionally, metal chelation using specific chelating agents may also be considered as an interventional approach [196]. Recent findings that persulfide and polysulfide can bind to cadmium thereby decreasing cadmium toxicity [197–199] may also provide potential approaches for counteracting cadmium-induced kidney injury.
