## 4 Discussion
To be applied as antioxidants in food systems, it is very urgent to take into consideration the optimum technological and processing factors, such as temperature and pH, affecting the stability [33]. The ROS/RNS scavenging capacity of all the herbal fractions was highly influenced by the pH of the system. All aqueous extracts were subjected to different pH systems (4, 7, and 9) to simulate acidic, neutral, and alkaline pH values. The outcomes illustrated the significant influence of pH on the antioxidant activity of herbal extracts. Most of the extracts were stable at pH 4. [PERSON] et al., 2020 suggested that in acidic conditions of aqueous extracts, phenolic content and antioxidant activity increase compared to a neutral aqueous system [67]. Drug-induced nephrotoxicity was established in the current investigation by a one-time intraperitoneal injection of acetaminophen on the 14 th day of the experiment. The toxicity was characterized by a significant (\(p<0.05\)) decrease in total protein content and tubule nephritis histological characteristics in the acetaminophen group (negative control) compared to untreated (group I) rats. However, pretreatment with daily, graded oral dosages of UD, CBP, and IR (groups III, IV, and V, respectively) for 14 days reduced these alterations in a dose-related manner. All of the extracts substantially (\(p<0.001\)) reduced the acute toxicity of APAP overdose, as evidenced by higher protein levels in kidney tissue homogenates, keeping their values within the normal range compared to the APAP-treated mice (group II). The examination of the significant weight change in the mice was equally remarkable. The weight of the mice normally increased among all the groups until day 14. Slight but significant weight loss was observed in the acetaminophen-treated group (negative control) compared to the control group. The groups pretreated with herbal extracts showed normal weight changes compared with the control group. The reason for the weight loss could be lethargy and reduced food consumption in the APAP group, which could also be associated with the intraperitoneal injection procedure of acetaminophen. Thus, the anorexia state of the nephotoxic mice could account for the significant, as well as progressive weight losses recorded for the acetaminophen-intoxicated mice [68]. The histological analysis of kidney tissue in the control group demonstrated proper morphology of the parenchyma of the kidneys, with no pathological findings. APAP administration, on the other hand, caused significant kidney damage, as evidenced by the shedding of necrotic tubular cells and necrotic cellular debris found in the intercellular spaces of both the proximal and distal convoluted tubules. In the medullary area, vacuolar degradation of the renal mucosa of the proximal tubule and hyaline casts were observed. In addition, there was significant compaction, infiltration of inflammatory cells, and edema in the interstitial tissue. The portion of the APAP-intoxicated kidney showed extensive disintegration, hematoma, and edema with lymphocyte infiltration. Remarkably, administration of UD, CBP and IR attenuated these pathological alterations, showing the extract's capacity to repair APAP-induced cell damage. This ameliorative behavior was evident by the normal cellular architecture of APAP-intoxicated groups pretreated with herbal fractions. UD and CBP seemed to be more ameliorative than IR, which was demonstrated by the minimal recovery of mice from group V (IR) from nephrotoxicity caused by APAP. Previous evaluations showed that the ethanolic extract of _U. dioica_ exhibited significant nephoprotective activity against gentamicin-induced nephrotoxicity in rabbits [69]. It was also documented that _Capsella bursa-pastoris_ has anti-inflammatory properties, as it inhibits the production of IL-6 and TNF-\(\alpha\) in the inflammatory development process, and Inula racemosa has adrenaline beta-blocking efficacy [70; 71].