**5. Application of natural antioxidant against F toxicity in different organs**

Studies have been carried out to explore natural antioxidants against toxic substances or elements [37, 38]. Antioxidant molecules are thought to play a crucial role in counteracting free-radical-induced damage to macromolecules [39]. There is a wide range of antioxidants that can counteract the condition of oxidative stress. It includes vitamins, phenolic compounds (flavonoids), and carotenoids. Minerals including selenium, zinc, manganese, magnesium, and copper also play a part in the body's hundreds of antioxidant functions. Aside from scavenging free radicals, natural antioxidants have been shown to influence the expression of several genes and signal regulatory pathways, potentially preventing cell death [40]. The natural antioxidants listed below were employed to alleviate F-induced oxidative stress-mediated damage in several organs in rats.

*Sources of Human Overexposure to Fluoride, Its Toxicities, and Their Amelioration Using… DOI: http://dx.doi.org/10.5772/intechopen.103714*

#### **5.1 Hesperidin against F hepato toxicity**

Recently, Caglayan et al. [41] reported that 600 ppm of fluoride administration induced the hepatotoxicity with severe damage in rats. However, hesperidins (HSP) 200 ppm administration to F group recovered completely from the F-induced toxicity in rats. The data showed the antioxidative potential of HSP on F-induced toxicity in liver tissue. Similarly, Küçükler et al. [42] also demonstrated the antioxidant property of HSP (100 mg/kg) in albino Wistar rats against F-induced hepatoxicity.

#### **5.2** *Prunella vulgaris* **against F nephrotoxicity**

Natural antioxidants can help to conquer oxidative stress and free-radical-induced disorders. In an earlier study, epigallocatechingallate (EGCG) depicted ameliorative effects toward F nephrotoxicity in rats [43]. However, a recent study from Li et al., [44] observed that the oral administration of *P. vulgaris* (1.575 g crud drug) attenuated the fluoride-induced oxidative toxicity in rat kidneys. The hole plants were dried and powdered and extracted (Ethanol 80%, Distilled water 20%) the drug by using reflux extraction apparatus. This result indicates that natural antioxidants exhibit the attenuating efficacy over xenobiotics of the toxic element on different organs. After extraction of PV drug, it was passed through a series of HPLC (high-performance liquid chromatography), to identified the natural bioactive compounds followed by structural identification of natural bioactive compounds by using XRD.

#### **5.3 Silymarin against F cardiotoxicity**

Milk thistle extract has a centuries-old history of use in Indian folk medicine to treat a variety of illnesses including jaundice, gallstones, hemorrhage, bronchitis, or varicose veins. Its beneficial effects have been attributed to the antioxidant, antiproliferative, and anti-inflammatory effects based on the regulation of specific signaling pathways. Nabavi et al. [45] reported that fluoride caused severe damage to the heart and brain tissue after administration. These effects are due to the alteration of enzymatic and non-enzymatic antioxidants with increased lipid peroxidation markers. This exploration shows that the Silymarin has the potential phytoremediation property against F-induced toxicity in rats.

#### **5.4 Curcumin against F** *in-vitro* **toxicity**

*Curcumin longa* is widely used as a food additive and was one of the bioactive natural products in phytoremediation therapy. In the traditional medicine of India, a cream of *Curcuma longa* called Ayurveda is used for the treatment of eye diseases, wounds, bites, burns, and various dermal diseases [46]. Fujiwara et al. [47] recently reported that the antioxidant efficacy of Curcumin in an in-vitro study against ameloblast LS8 cells treated with fluoride toxicity. In this study, Curcumin significantly attenuated the F toxicity on ameloblast LS8 cells due to the potent phytotherapeutic property of curcumin and its derivatives.

#### **5.5 Quercetin against F neuro toxicity**

Quercetin is one of the best-studied polyphenols found in onions, apples, berries, tea, and red wine. It prevents apoptosis, anticancer, anti-inflammatory, and cardiovascular

protective ability via its potent antioxidant properties [48]. Chouhan et al. [49] reported that Silymarin and Quercetin synergistically abrogated fluoride-induced oxidative toxic effect in rat liver and kidney via activation of phase I antioxidant enzymes such as SOD, CAT, GPx. Similarly, Nabavi et al. [50] reported that Quercetin showed preventive effect of fluoride toxicity in the brain due to the high concentration of antioxidant capacity of Quercetin to abrogates the Fl-induced ROS in different organs.
