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Fish Oil's Preventive Effect on Two-Stage Skin Carcinogenesis in Swiss Albino Mice: Involvement of NF-ҝB Pathways and
Hayeme Cheniti1, Assia Kadi1, Rym Agred2
1Laboratory of Biochemistry and Environmental Toxicology, Badji Mokhtar-Annaba University, Annaba, Algeria.
Abstract:
This study investigated the chemopreventive mechanisms of fish oil (FO) at different doses and administration routes in skin carcinogenesis induced by 7,12-dimethylbenz[a]anthracene (DMBA) and croton oil (CO) in Swiss albino mice. Seventy mice were divided into 10 groups, including controls and those receiving FO either orally or topically, with or without the carcinogenesis protocol. Warts were morphologically analyzed. Anatomopathological analysis, qRT-PCR of nuclear factor kappa B (NF-қB) subunits' gene expression, and evaluation of oxidative parameters were conducted. Anatomopathological analysis revealed a presence of invasive squamous cell carcinoma (SCC) in DMBA group. Both oral (500 mg/kg/day) and topical FO treatment showed no signs of cancer, while oral administration at 50 mg/kg/day had no therapeutic effect, and 250 mg/kg/day resulted in low-grade malignancy. Both oral (250 and 500 mg/kg/day) and topical FO significantly reduced NF-кB1 gene expression, alleviated oxidative stress markers, and restored antioxidant enzyme activities compared to the DMBA group. FO shows dose-dependent chemopreventive effects, with oral administration potentially as effective as topical application when using an appropriate dosage. The development of SCC is linked to the stress status and the upregulation of the canonical NF-κB pathway, while FO's chemoprotective effects likely result from its downregulation.
Insights
Fish oil (FO) demonstrates dose-dependent chemopreventive effects against skin cancer. Optimal oral or topical FO dosages significantly reduced cancer development by downregulating nuclear factor kappa B (NF-κB) and alleviating oxidative stress.
Area of Science:
- Biochemistry
- Dermatology
- Pharmacology
Background:
- Skin carcinogenesis is a complex process involving genetic and environmental factors.
- The nuclear factor kappa B (NF-κB) pathway and oxidative stress are implicated in skin cancer development.
- Chemoprevention strategies aim to prevent or delay cancer initiation and progression.
Purpose of the Study:
- To investigate the chemopreventive mechanisms of fish oil (FO) in a mouse model of skin carcinogenesis.
- To evaluate the effects of different doses and administration routes of FO on tumor development.
- To assess the impact of FO on NF-κB pathway activation and oxidative stress markers.
Main Methods:
- Induction of skin carcinogenesis using 7,12-dimethylbenz[a]anthracene (DMBA) and croton oil in Swiss albino mice.
- Administration of fish oil (FO) orally or topically at various doses.
- Morphological and anatomopathological analysis of skin lesions.
- Quantitative real-time PCR (qRT-PCR) for NF-κB gene expression.
- Assessment of oxidative stress and antioxidant enzyme activities.
Main Results:
- DMBA treatment induced invasive squamous cell carcinoma (SCC).
- High-dose oral (500 mg/kg/day) and topical FO prevented cancer development.
- Lower oral doses of FO showed limited or no therapeutic effect.
- FO treatment significantly reduced NF-κB1 gene expression and oxidative stress markers.
- FO treatment restored antioxidant enzyme activities.
Conclusions:
- Fish oil exhibits dose-dependent chemopreventive properties against skin carcinogenesis.
- Oral administration of FO can be as effective as topical application with appropriate dosing.
- FO's chemoprotective effects are mediated by the downregulation of the NF-κB pathway and reduction of oxidative stress.
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