## 4 Discussion  
Artesunate metabolism has been reported to involve a release of reactive oxygen species (ROS) which may lead to oxidative stress [27, 28]. Artesunate also induces DNA damage resulting in the formation of DNA adducts [29]. This study evaluated the effects of hydroethanolic extract of _S. aromaticum_ buds (cloves) on lipid and antioxidant levels of artesunate-challenged Wistar rats. Usually, the most important and viable first line of defense in combating oxidative damage is through the use of erythrocyte endogenous antioxidants such as superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) [30, 31]. They help in the conversion of peroxides and hydroperoxides to water and oxygen molecules which are subsequently removed from the cells without the risk of causing molecular damage. Reduced glutathione is an antioxidant which confers bio-protection on cells. Reduced glutathione has effective protection against toxic effects of substances on tissues [32, 33]. The human system stores about 90% of its glutathione pool in reduced form (GSH). Increase in catalase levels may be due to a reduction in ROS which promotes resistance to acute oxidative stress from peroxide [34]. This study observed significant reductions in the activities of antioxidant enzymes (CAT, SOD, and GPx) in the artesunate-induced group, which suggests possible accumulations in ROS levels. However, groups treated with HESAB showed considerably higher levels of CAT, SOD, and GPx activities and reversed the toxic effects of artesunate. This finding is in agreement with [PERSON] et al. [35] who reported that clove buds are good sources of natural antioxidants. Meanwhile, CAT, SOD, and GPx have been shown to be functionally related in physiological system. SOD transforms superoxide anion into hydrogen peroxide (H\({}_{2}\)O\({}_{2}\)) and molecular oxygen (O\({}_{2}\)). Then both catalase and peroxididases convert H\({}_{2}\)O\({}_{2}\) into water. A decrease in SOD activity suggests a decrease in the intracellular H\({}_{2}\)O\({}_{2}\) concentration and resultant decreases in the activities of CAT and GPx [36]. Restoration of antioxidant status could be through the free radical scavenging mechanism in which the clove constituents served as electron donors to the radicals emanating from artesunate stress. \begin{table}
\begin{tabular}{c c c c} \hline \hline
**Parameters/** & **MDA (μmol/L)** & **NO (μmol/L)** & **GSH (μmM)** \\
**Group** & & & \\ \hline Control & 2.237 \(\pm\) 0.95 & 6.20 \(\pm\) 2.21 & 0.49 \(\pm\) 0.068 \\ ART only & 5.032 \(\pm\) 1.25 a,c,d,e,f & 10.65 \(\pm\) 3.84 c,e & 0.20 \(\pm\) 0.145 a  \\
400 mg/kgbw HESAB & 1.763 \(\pm\) 0.58 & 4.54 \(\pm\) 1.33 & 0.41 \(\pm\) 0.023 \\
800 mg/kgbw HESAB & 1.981 \(\pm\) 0.67 & 4.06 \(\pm\) 0.98 & 0.45 \(\pm\) 0.12 \\ ART + 400 mg/kgbw HESAB & 2.271 \(\pm\) 0.91 & 5.64 \(\pm\) 1.76 & 0.38 \(\pm\) 0.19 \\ ART + 800 mg/kgbw HESAB & 2.609 \(\pm\) 0.56 & 7.32 \(\pm\) 2.17 & 0.33 \(\pm\) 0.21 \\ \hline \hline \end{tabular} GSH—glutathione ART—artesunate; MDA—malondialdehydedehyde; NO=mitric oxide. Values were expressed as mean \(\pm\) SD (n = 8). Superscripts a, c, d, e, and indicate significant difference (\(p<\) 0.05).  
\end{table} 
Table 4: Effect of HESAB on oxidative stress biomarkers. Furthermore, elevated levels of MDA and NO are also indicators of lipid peroxidation and oxidative stress [37; 38] with MDA resulting from the end product of polyunsaturated fatty acid peroxidation. In both human and animal models, elevated levels of MDA are associated with hyperlipidemia and reduced antioxidant levels in the experimental subjects [39]. This finding corroborates [PERSON] et al. [2] who showed that rats challenged with artesunate had a significant increase in MDA and NO levels. However, administration of HESAB was sufficient to lower the free radicals. Findings from this study have also shown that artesunate toxicity could alter lipid metabolism.