Melatonin improves periodontitis‐induced kidney damage by decreasing inflammatory stress and apoptosis in rats

Abstract

Background Two main aims of this animal study were to inspect the possible effects of periodontitis on the structure and functions of the kidneys and the therapeutic effectiveness of melatonin. Methods Twenty‐four male Sprague‐Dawley rats were randomly divided into three groups: control, experimental periodontitis (Ep), and Ep‐melatonin (Ep‐Mel). Periodontitis was induced by placing 3.0‐silk sutures sub‐paramarginally around the cervix of right‐left mandibular first molars and maintaining the sutures for 5 weeks. Then melatonin (10 mg/kg body weight/day, 14 days), and the vehicle was administered intraperitonally. Mandibular and kidney tissue samples were obtained following the euthanasia. Periodontal bone loss was measured via histological and microcomputed tomographic slices. On right kidney histopathological and immunohistochemical, and on the left kidney biochemical (malonyl‐aldehyde [MDA], glutathione, oxidative stress [OSI], tumor necrosis factor [TNF]‐α, interleukin [IL]‐1β, matrix metalloproteinase [MMP]‐8, MMP‐9, and cathepsin D levels) evaluations were performed. Renal functional status was analyzed by levels of serum creatinine, urea, cystatin‐C, and urea creatinine. Results Melatonin significantly restricted ligature‐induced periodontal bone loss (P <0 .01) and suppressed the levels of proinflammatory cytokines (TNF‐α and IL‐1β), oxidative stress (MDA and OSI), and proteases (MMP‐8, MMP‐9, and CtD) that was significantly higher in the kidneys of the rats with periodontitis (P <0.05). In addition, periodontitis‐related histological damages and apoptotic activity were also significantly lower in the Ep‐Mel group (P <0.05). However, the markers of renal function of the Ep group were detected slightly impaired in comparison with the control group (P >0.05); and the therapeutic activity of melatonin was limited (P >0.05). Conclusion Melatonin restricts the periodontitis‐induced inflammatory stress, apoptosis, and structural but not functional impairments.

Periodontitis exacerbates the renal degenerative effects of obesity in rats

“…with significant increases in MDA, TOS, and OSI associated with kidney damage in rats with experimental periodontitis. 12 Similarly, França et al 13 reported an increase in kidney MDA and OSI levels in rats with periodontitis, and Tomofuji et al 38 reported a higher level of kidney oxidative stress in experimental periodontitis. The results of the present study, consistent with the aforementioned studies, showed higher levels of oxidative stress in the experimental periodontitis group that could be associated with kidney damage.…”

“…24,25 It is yet unknown exactly with which mechanisms periodontitis increases the risk of kidney disease. This phenomenon has been sought to be explained by the possible effects of oxidative stress 12,13 or systemic inflammatory changes. 7 In both human 35 and animal, 36,37 studies reported that levels of oxidative status parameters such as MDA, GSH, and OSI(TOS/TAS) change, and especially, the levels of OSI, TOS, and MDA increase in kidney damage.…”

“…Then, the all animals were euthanized by lethal injection of pentobarbital (50 mg/kg BW). 12,29 Both the kidneys and the mandibular tissues including the first molars were dissected bilaterally with the surrounding tissue. The right kidney samples were transferred to 10% neutral formaldehyde solution for histopathological and histochemical analyses.…”

“…7,8 In the literature, the relationship between periodontitis and kidney diseases was sought to be explained by clinical [9][10][11] and experimental [12][13][14] studies. In some of these studies, 12,13 it was shown that periodontitis may increase the susceptibility to chronic kidney disease while in others, 10,15 it was shown that kidney diseases may possibly increase the risk and prevalence of periodontitis. In a study on rats, França et al 13 reported that periodontitis may lead to a predisposition to kidney disease, which may be mediated by increased oxidative stress.…”

Periodontitis Exacerbates and Promotes the Progression of Chronic Kidney Disease Through Oral Flora, Cytokines, and Oxidative Stress

“…It can be assumed that the development and progression of periodontitis can lead to changes in the form of renal tissue. In another study, three groups of male Wistar rats had their upper molars ligated for 3 weeks to induce periodontitis ( Kose et al, 2020 ). One group of rats was treated with melinjo resveratrol, one without resveratrol, and the other was a control group with no periodontitis or resveratrol treatment.…”