PLoS ONE., 2021., 16(10): e0258800.

Effect of flaxseed on systemic inflammation and oxidative stress in diabetic rats with or without chronic kidney disease.

Al Za’abi M Ali H Ali BH


Background – Diabetes mellitus (DM) and chronic kidney disease (CKD) are common causes of morbidity and mortality. Flaxseed contains several bioactive compounds that have been shown to possess anti-inflammatory and antioxidative properties. The aim of the present study was to investigate the possible effect of flaxseed in diabetic rats with adenine–induced CKD. Methods – Male Wister rats (n = 48) were randomly divided into seven equal groups and treated for 33 consecutive days as follows: G1: control. G2 adenine, G3: streptozotocin (STZ), G4: flaxseed, G5: adenine+flaxseed, G6: STZ+flaxseed, G7: adenine+STZ+flaxseed). DM or CKD were experimentally induced by a single intraperitoneal injection of streptozotocin (STZ) or by adenine via oral gavage, respectively. Results – Rats fed adenine alone exhibited several changes including decreased body weight, increased food and water intake and urine output, increased urinary albumin/creatinine ratio. They also showed an increase in plasma urea and, creatinine, indoxyl sulfate, neutrophil gelatinase-associated lipocalin and cystatin C, and a decrease in renalase activity. These were associated with significant changes in inflammatory and oxidative biomarkers, e.g., increase in 8-isoprostane, 8 -hydroxy -2-deoxy guanosine and decrease in antioxidant enzymes, as well as increase in interleukins 1β and 6, and NF-κB, and a decrease in interlukin-10. Histopathologically, there was increased tubular necrosis and fibrosis. Concomitant administration of adenine and STZ further worsened the renal damage induced by adenine alone. Flaxseed significantly ameliorated the changes caused by adenine and STZ, given either singly or in combination.

Conclusion – These findings suggest that flaxseed is a potential therapeutic agent in attenuating the progression of CKD in diabetes.

Key Points

Flaxseed has been found to affect gut functions and lipid metabolism in rats and possess an antihypertensive effect via the modulation of endogenous enzymes in deoxycorticosterone acetate induced renal hypertension in rats. In the kidney, flaxseed oil reduced the renal injury in experimental polycystic kidney disease. It also decreased the C-reactive protein and inflammation in chronic hemodialysis patients.

In this study, it was examined the effects of flaxseeds on experimentally induced diabetes in rats with or without experimentally induced CKD. Flaxseed in this study enhanced the TAC, SOD, and catalase activities, possibly through the upregulation of the genes expressing these enzymes. The increase in these enzyme activities might have led to a reduction in the direct oxidative and peroxidative markers 8-OHdG and 8-isoprostane, respectively. It is also possible that flaxseed downregulated the genes expressing these markers. The modulation of oxidative stress by flaxseed was reflected indirectly in the improvement in the creatine clearance and the concentration of other biochemical markers such as indoxyl sulfate, NAG, renalase, cystatin C and NGAL.

At the histopathological level, flaxseed reduced both the tubular necrosis and fibrosis induced by adenine and/or STZ. Such findings at the tissue level confirm the beneficial role of flaxseed in reducing the inflammatory and oxidative reactions associated with diabetes and CKD.

The effects shown in the current experimental study verified that flaxseed effectively mitigated nearly all the physiological, biochemical, and histopathological alterations caused by adenine and/or STZ which suggest that it can be considered a potentially useful dietary supplement in the management of diabetic induced-CKD. The antioxidant and anti-inflammatory properties of flaxseed have been used to mitigate inflammatory and oxidative cascades in some human diseases.

In conclusion, the results suggest that flaxseed can be a potential therapeutic agent for the treatment of diabetes-induced CKD. Further studies either at the translational level or small-scale clinical trials might be warranted to confirm such findings.