# Impact of Fish Oil and Flaxseed Oil on HIF‐2α, COX‐2 and IFN‐γ Protein Expression: A Case Study in Rats With Kidney Damage Due to Circadian Rhythm Disorder

## TL;DR

This study shows that fish oil and flaxseed oil can reduce kidney damage and inflammation in rats with disrupted circadian rhythms.

## Contribution

The study demonstrates the anti-inflammatory and kidney-protective effects of fish oil and flaxseed oil in a circadian rhythm disruption model.

## Key findings

- Fish oil and flaxseed oil reduced levels of HIF-2α, COX-2, and IFN-γ in rats with circadian rhythm disruption.
- These oils improved kidney pathology and reduced inflammation markers in the animal model.
- The results suggest that omega-3 fatty acids may be effective in mitigating kidney damage caused by circadian rhythm disruption.

## Abstract

This study set out to investigate kidney damage by examining the levels of key proteins‐HIF‐2α, COX‐2 and IFN‐γ in rats with disrupted circadian rhythms. It also explored how fish oil and flaxseed oil might influence the intensity of inflammation and its effects on kidney health.

Circadian rhythm disorder model groups consisted of eight rats each. Except for the control group, other groups (circadian rhythm, flaxseed oil and fish oil groups) were exposed to an adjustable light/dark cycle for 19 days, while the control group was kept on a standard light/dark cycle. In addition to standard food and water ad libitum nutrition for 19 days in four groups, 1000 mg/kg/day flaxseed oil was given to the flaxseed oil group and 400 mg/kg/day fish oil was given to the fish oil group by gavage for 19 days. Histological lesions in tissues were evaluated by Haematoxylin–Eosin staining and using a sequential grading system. For immunohistochemical analysis, IFN‐γ, COX‐2 and HIF‐2 antibodies were used to evaluate the degree of immunohistochemical reactivity of the cells.

Nutrition unequivocally plays a critical role in regulating circadian rhythms, as factors such as meal timing, nutrient composition and gut health directly influence the body's internal clock and overall rhythm stability. Omega‐3 fatty acids are known to influence immune, inflammatory and neurological pathways‐all of which are controlled by the circadian clock. When circadian rhythms are disrupted, key signalling proteins such as HIF‐2α, COX‐2 and IFN‐γ become dysregulated, leading to potential kidney damage. Remarkably, treatments with fish oil and flaxseed oil have been shown to reduce inflammation markers, effectively mitigating kidney damage and offering significant anti‐inflammatory benefits. These results emphasize the aptitude of incorporating fish oil and flaxseed oil into the diet as a powerful strategy to combat kidney damage and slow the pathological effects caused by circadian rhythm disruption.

Circadian rhythm disturbances are associated with various health problems, including kidney damage characterized by microhaemorrhage and inflammatory cell infiltration. In this study, fish oil and flaxseed oil demonstrated protective, anti‐inflammatory effects by reducing levels of HIF‐2α, COX‐2 and IFN‐γ and improving kidney pathology. These effects were evaluated within the scope of an animal model, and the findings provide valuable preliminary data for future human studies.

1. This investigation divulges how disruption in circadian rhythms lead to the disequilibrium of critical signalling proteins like HIF‐2α, COX‐2 and IFN‐γ, contributing to kidney damage and inflammation.

2. Treatment with omega‐3 rich fish oil and flaxseed oil significantly reduced inflammation markers and kidney damage, demonstrating their potential as effective nutritional interventions for combating kidney inflammation.

3. The findings underscore the importance of incorporating fish oil and flaxseed oil into the diet, offering a promising approach to mitigate kidney damage and slow the progression of inflammation caused by disrupted circadian rhythms.