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RESEARCH PAPER
Prosopis africana protects against heavy metal mixture-induced pulmonary and hematological toxicity via nuclear factor erythroid 2-related factor 2/nuclear factor-kappa B/caspase-3 signaling
1
African Centre of Excellence for Public Health and Toxicological Research, University of Port Harcourt, Choba, Nigeria
2
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Enugu State University of Science and Technology, Enugu, Nigeria
3
Department of Experimental Pharmacology and Toxicology, Faculty of Pharmaceutical Sciences, University of Port Harcourt, Port Harcourt, Nigeria
4
Advanced Research Centre, European University of Lefke, Lefke, Northern Cyprus
Submission date: 2025-11-27
Final revision date: 2026-03-02
Acceptance date: 2026-06-02
Publication date: 2026-09-09
Corresponding author
KEYWORDS
Prosopis africanaheavy metal toxicityNrf2/NF-κB/caspase-3 signalingoxidative stresshematotoxicitymetal bioaccumulation
TOPICS
ABSTRACT
Background:
Heavy metal mixture (HMM) exposure poses severe health risks by inducing oxidative stress and inflammation. The limitations of conventional chelation therapy necessitate exploring natural alternatives. Although Prosopis africana (PA) has antioxidant properties, its potential as a protective agent remains underexplored. This study investigated the protective mechanisms of PA against lead/ cadmium/arsenic-induced pulmonary and hematological toxicity.
Material and methods:
Rats were treated with HMM alone or combined with PA (500, 1000, or 1500 mg/kg). The evaluated parameters included lung and blood metal accumulation, oxidative stress markers (malondialdehyde, nitric oxide), antioxidant defenses (superoxide dismutase, catalase, reduced glutathione, glutathione peroxidase), inflammatory cytokines (interleukin 6 [IL-6], tumor necrosis factor alpha [TNF-α]), transcription factors (nuclear factor erythroid 2-related factor 2 [Nrf2], nuclear factor kappa B [NF-κB]), caspase-3, hematological parameters, and lung histopathology. Multivariate analyses were applied to integrate biomarker patterns.
Results:
HMM exposure significantly increased tissue metal levels, oxidative stress, inflammatory mediators, and caspase-3 activity, while suppressing antioxidant defenses and disrupting hematological parameters and lung architecture. PA co-treatment reversed these changes in a dose-dependent manner. At 1500 mg/kg, PA reduced blood metal levels by > 90%, normalized the oxidative-antioxidant balance, decreased IL-6 and TNF-α by 60–70%, suppressed caspase-3 activity by 90%, restored hematological indices, and ameliorated lung damage. Principal component and hierarchical cluster analyses clearly separated the HMM-exposed groups from the PA-treated groups based on their distinct oxidative, inflammatory, and protective profiles.
Conclusions:
PA protects against HMM-induced toxicity by reducing metal bioavailability – potentially via chelation and/or altered absorption or excretion – coupled with Nrf2 activation and NF-κB/caspase-3 suppression. These findings suggest its potential as an adjunct therapy for heavy metal-induced pathologies.
Heavy metal mixture (HMM) exposure poses severe health risks by inducing oxidative stress and inflammation. The limitations of conventional chelation therapy necessitate exploring natural alternatives. Although Prosopis africana (PA) has antioxidant properties, its potential as a protective agent remains underexplored. This study investigated the protective mechanisms of PA against lead/ cadmium/arsenic-induced pulmonary and hematological toxicity.
Material and methods:
Rats were treated with HMM alone or combined with PA (500, 1000, or 1500 mg/kg). The evaluated parameters included lung and blood metal accumulation, oxidative stress markers (malondialdehyde, nitric oxide), antioxidant defenses (superoxide dismutase, catalase, reduced glutathione, glutathione peroxidase), inflammatory cytokines (interleukin 6 [IL-6], tumor necrosis factor alpha [TNF-α]), transcription factors (nuclear factor erythroid 2-related factor 2 [Nrf2], nuclear factor kappa B [NF-κB]), caspase-3, hematological parameters, and lung histopathology. Multivariate analyses were applied to integrate biomarker patterns.
Results:
HMM exposure significantly increased tissue metal levels, oxidative stress, inflammatory mediators, and caspase-3 activity, while suppressing antioxidant defenses and disrupting hematological parameters and lung architecture. PA co-treatment reversed these changes in a dose-dependent manner. At 1500 mg/kg, PA reduced blood metal levels by > 90%, normalized the oxidative-antioxidant balance, decreased IL-6 and TNF-α by 60–70%, suppressed caspase-3 activity by 90%, restored hematological indices, and ameliorated lung damage. Principal component and hierarchical cluster analyses clearly separated the HMM-exposed groups from the PA-treated groups based on their distinct oxidative, inflammatory, and protective profiles.
Conclusions:
PA protects against HMM-induced toxicity by reducing metal bioavailability – potentially via chelation and/or altered absorption or excretion – coupled with Nrf2 activation and NF-κB/caspase-3 suppression. These findings suggest its potential as an adjunct therapy for heavy metal-induced pathologies.
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