**1. Introduction**

Resveratrol (3,4 ,5-trihydroxy-trans-stilbene) is a polyphenol found in a group of stilbenes. It has high antioxidant potential associated with beneficial health effects in the context of neurodegenerative and cardiovascular diseases, as well as some types of cancer, diabetes, and obesity-related disorders [1,2]. The antioxidant effects of resveratrol have been attributed to its ability to scavenge reactive oxygen species (ROS), activate repair mechanisms, and induce apoptosis [3,4]. Notably, resveratrol has been found to prevent DNA damage [5,6]. Although the effects of resveratrol on toxicity induced by metals (e.g., arsenic trioxide, sodium arsenite, copper oxide, chromic chloride, and potassium dichromate) have been examined in rodent hearts, livers, kidneys, thymus, and ovaries [7–11], there are no studies evaluating the effects of this polyphenol on hexavalent chromium [Cr(VI)] compound-induced genotoxicity.

**Citation:** Nicolás-Méndez, T.; Kacew, S.; Ortiz-Muñiz, A.R.; Mendoza-Núñez, V.M.; García-Rodríguez, M.d.C. Protective Effect of Resveratrol against Hexavalent Chromium-Induced Genotoxic Damage in Hsd:ICR Male Mice. *Molecules* **2022**, *27*, 4028. https://doi.org/10.3390/ molecules27134028

Academic Editor: Nour Eddine Es-Safi

Received: 20 May 2022 Accepted: 21 June 2022 Published: 23 June 2022

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Cr(VI) is largely released into the environment due to industrial activities, mainly including electroplating, welding, leather tanning, and pigment manufacturing, or found in automobile exhaust and tobacco products [12,13]. Both acute and chronic exposure to Cr(VI) compounds have been associated with cancer induction in different organs and tissues [14,15]. The genotoxic damage produced during its intracellular reduction may initiate and promote Cr(VI)-induced carcinogenesis by the formation of DNA adducts, cross-linking (DNA-protein and DNA-DNA), abasic sites, and oxidized DNA bases [16]. It is important to highlight that the induction of apoptosis, the inhibition of repair mechanisms, and gene expression play a crucial role in the genotoxic damage generated by exposure to Cr(VI) compounds [15,17]. Several studies have shown that antioxidants can counteract the effects of ROS and free radicals [18], such that antioxidant-rich substances have emerged as potential agents for preventing and adjuvating oxidative stress and DNA damage [19–21]. More precisely, compounds such as polyphenols have been shown to play a direct role as radical scavengers and metal chelators and to exert indirect effects by modulating levels of transcription factors and enzymes [22–24]. Therefore, the aim of the present study was to examine the protective effects of resveratrol against Cr(VI)-induced genotoxicity in vivo and the underlying metabolic processes including 8-hydroxydeoxyguanosine (8-OHdG, 7,8-dihydro-8-oxodeoxyguanosine) adduct repair, the endogenous antioxidant component system, and apoptosis, which may be involved in preventing Cr(VI)-induced DNA damage.

#### **2. Results**
