# Comprehensive dose-dependent hepatorenal protective effects of Ziziphus nummularia leaf extract against quinolphos-induced toxicity in Wistar rats

**Authors:** Ramya Rengaraj, Stalin Arumugam, Praveen Kumar Dharmaraj, Varadharajan Gokula, Aarthi Murugavel, Mohamed Saiyad Musthafa, Cristiana Roberta Multisanti, Caterina Faggio

PMC · DOI: 10.3389/fphar.2026.1777534 · Frontiers in Pharmacology · 2026-02-19

## TL;DR

This study shows that Ziziphus nummularia leaf extract can protect the liver and kidneys of rats from quinolphos toxicity in a dose-dependent manner.

## Contribution

The study demonstrates the dose-dependent hepatorenal protective effects of Ziziphus nummularia leaf extract against quinolphos-induced toxicity in Wistar rats.

## Key findings

- High-dose Z. nummularia extract nearly fully restored kidney and liver histopathology in quinolphos-treated rats.
- Z. nummularia extract improved behavioral impairments and restored appetite and activity levels in treated rats.
- All treatment groups showed 100% survival, with no mortality observed during the experimental period.

## Abstract

Quinolphos pose considerable hepatorenal toxicity risks, potentially necessitating the investigation of natural protective agents. This study assessed the pharmacological effects of Z. nummularia leaf extract in mitigating quinolphos-induced toxicity in male Wistar rats (n = 30) through comprehensive histopathological and behavioural evaluations. Animals were randomly divided into five groups: control, quinolphos-induced, vehicle control (300 mg/kg), and two treatment groups receiving Z. nummularia leaf extract at low dose (250 mg/kg) and high dose (500 mg/kg).The quinolphos-treated group displayed severe behavioural impairments, characterised by reduced locomotor activity, coarse coat texture, and substantial weight loss, with extensive histopathological damage in hepatic and renal tissues. Kidney sections exhibited significant glomerular cell debris and atrophy, abnormalities in the basement membrane, tubular degeneration, interstitial oedema, and tubular necrosis. The liver examination revealed significant changes in hepatocyte morphology, portal structures, leukocyte infiltration, sinusoidal congestion, and hepatocyte necrosis. The administration of Z. nummularia extract exhibited notable dose-dependent protective effects. The high-dose group demonstrated nearly complete histopathological recovery, with no detectable glomerular debris, tubular injury, or tubular necrosis in the kidneys, minimal hepatocyte changes, and total restoration of vascular integrity in liver tissue. Behavioural enhancements correlated with histopathological observations, reflecting a gradual restoration of appetite, activity levels, and overall clinical status. All treatment groups exhibited 100% survival during the experimental period. These findings reveal substantial evidence validating the pharmacological effects of Z. nummularia as a natural hepatoprotective and nephroprotective agent against organophosphate-induced organ damage.

## Linked entities

- **Chemicals:** Quinolphos (PubChem CID 26124)

## Full-text entities

- **Genes:** Bche (butyrylcholinesterase) [NCBI Gene 65036]
- **Diseases:** behavioural impairments (MESH:D001523), oedema (MESH:C536897), organ toxicity (MESH:D019965), neurotoxic (MESH:D020258), TN (MESH:D007683), gastrointestinal disorders (MESH:D005767), tubular injury (MESH:D000230), behavioural deficits (MESH:D001289), hepatorenal damage (MESH:D006530), toxicity (MESH:D064420), weight loss (MESH:D015431), anorexia (MESH:D000855), interstitial edema (MESH:D004487), GA (MESH:D001284), inflammation (MESH:D007249), behavioural abnormalities (MESH:D000014), pain (MESH:D010146), PD (MESH:D010300), mitochondrial dysfunction (MESH:D028361), neurological dysfunction (MESH:D009461), Renal histopathological alterations (MESH:D006030), coat dullness (MESH:D058456), fever (MESH:D005334), necrosis (MESH:D009336), clinical abnormalities (MESH:D013568), hyperactivity (MESH:D006948), cognitive deficits (MESH:D003072), chronic diseases (MESH:D002908), bile duct abnormalities (MESH:D001649), TD (MESH:D009410), multi-organ damage (MESH:D000092124), hepato-renal toxicity (MESH:D007674), fatigue (MESH:D005221), hepatocellular damage (MESH:D056486), acute kidney injuries (MESH:D058186), liver disorders (MESH:D017093)
- **Chemicals:** pyrethroids (MESH:D011722), xylene (MESH:D014992), wax (MESH:D014885), tannins (MESH:D013634), sodium pentobarbital (MESH:D010424), Z. nummularia extract (-), OP (MESH:D010755), Paraffin (MESH:D010232), H&amp;E (MESH:D006371), 3-methylsalicylic acid (MESH:C503864), salt (MESH:D012492), haematoxylin (MESH:D006416), eosin (MESH:D004801), alkaloids (MESH:D000470), formalin (MESH:D005557), ethanol (MESH:D000431), flavonoids (MESH:D005419), ROS (MESH:D017382), saponins (MESH:D012503), water (MESH:D014867), cyclotrisiloxane hexamethyl (MESH:C024035), O, O-diethyl O-quinoxalin-2-yl phosphorothioate (MESH:C009145), lipid (MESH:D008055)
- **Species:** Ziziphus nummularia (species) [taxon 498071], Rattus norvegicus (brown rat, species) [taxon 10116], Ziziphus (genus) [taxon 72171], Cosavirus F (no rank) [taxon 2003652], Homo sapiens (human, species) [taxon 9606], Glycine max (soybean, species) [taxon 3847]
- **Mutations:** C-56  C, C +- 2  C

## Full text

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## Figures

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## References

61 references — full list in the complete paper: https://tomesphere.com/paper/PMC12960635/full.md

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Source: https://tomesphere.com/paper/PMC12960635