10-Dehydrogingerdione Attenuates Tramadol-Induced Nephrotoxicity by Modulating Renal Oxidative Stress, Inflammation and Apoptosis in Experimental Rats: Role of HO-1 Activation and TLR4/NF-κB/ERK Inhibition

Elnagar, Gehad M.; Elseweidy, Mohamed M.; Mahmoud, Yasmin K.; Elkomy, Nesreen M.I.M.; Althafar, Ziyad M.; Alnomasy, Sultan F.; Al-Gabri, Naif A.; Shawky, Mohamed

doi:10.3390/ijms23031384

Cited by 8 publications

(10 citation statements)

References 33 publications

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Section: Discussionsupporting

confidence: 93%

“…In agreement with our results, previous studies have shown that TRA significantly increased serum levels of CR and urea while decreasing serum levels of Alb [6], indicating its potential renal damage and impaired kidney function. The elevation in blood urea levels could also be caused by the destruction of red blood cells or the presence of toxic compounds [6,11,34]. The moderate presence of hyaline casts and severe necrosis found in the histopathology of kidney tissue, consistent with these biochemical findings, can explain why TRA negatively affected nephron function and caused kidney damage.…”

Section: Discussionsupporting

confidence: 93%

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High-Intensity Interval Training Ameliorates Tramadol-Induced Nephrotoxicity and Oxidative Stress in Experimental Rats

Sadat Hosseini,

Shirazpour,

Zangiabadizadeh

et al. 2024

Cureus

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Introduction: Tramadol (TRA) is an opioid analgesic widely prescribed for moderate-to-severe pain; however, its abuse and chronic use have been associated with kidney damage. Considering the protective role of exercise training in reducing organ damage, this study aimed to assess the influence of high-intensity interval training (HIIT) on a male rat's kidney following chronic TRA administration. Methods: In this experimental study, 30 male Wistar rats were assigned to the following groups: control (CON; animals received normal saline five days a week in the first month and three days a week in the second month), exercise (EXE; animals conducted HIIT training according to exercise protocol five days a week for two months), TRA (animals received TRA 50 mg/kg (i.p.) as described for the CON group), EXE-TRA (animals received TRA and conducted exercise protocol), and EXE-SL (animals received normal saline and conducted exercise protocol). Then, serum IL-6 and IL-10 levels, tissue malondialdehyde (MDA), total antioxidant capacity (TAC), glutathione peroxidase (GPx), superoxide dismutase (SOD), and levels of albumin, urea, and creatinine (CR), along with pathological changes in the kidney, were measured. A p-value of <0.05 was considered significant using GraphPad Prism v.9 (GraphPad Software, La Jolla, California, USA). Results: The inflammatory cytokines IL-6 and IL-10 were significantly increased in the EXE and EXE-TRA groups compared to the TRA group. Chronic administration of TRA in the TRA group decreased antioxidant indicators TAC, GPx, and SOD in kidney tissue while increasing oxidative stress MDA compared to the CON group (p<0.05). In contrast, the EXE-TRA group showed higher levels of TAC, GPx, and SOD, while MDA decreased compared to the TRA group. Additionally, serum levels of urea and CR were increased in the TRA group compared to the CON group, whereas these levels were decreased in the EXE-TRA group compared to the TRA group. The inflammatory effect of HIIT training, due to severe hyperemia and mild inflammatory cell infiltration, was seen in all EXE groups. Pathological findings confirmed TRA-induced kidney damage through moderate hyaline cast presence and severe apoptosis in the TRA group. Other findings were in line with the above results. Conclusion: These findings confirm the nephrotoxicity of chronic use of TRA through biochemical and oxidative markers and pathological outcomes. In addition, the result suggests that HIIT has the potential to mitigate the detrimental effects of TRA through reversing biochemical and oxidative markers, including TRA-induced apoptosis. Consequently, considering its restorative properties, HIIT could be explored as a prospective nephroprotective approach for long-term TRA treatment.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 93%

High-Intensity Interval Training Ameliorates Tramadol-Induced Nephrotoxicity and Oxidative Stress in Experimental Rats

Sadat Hosseini,

Shirazpour,

Zangiabadizadeh

et al. 2024

Cureus

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show abstract

“…In agreement to our results, previous studies showed that tramadol signi cantly increased serum levels of creatinine and urea while it decreased serum level of albumin (49) indicating its potential renal damage and impaired kidney function. The rise in blood urea levels could also be caused by the destruction of red blood cells or the presence of toxic compounds (12,15,49,50).…”

Section: Discussionsupporting

confidence: 93%

High Intensity Interval Training (HIIT) Ameliorates the Tramadol-Induced Nephrotoxicity and Oxidative Stress in Experimental Rats

Hosseini,

Meymandi,

Sepehri

et al. 2023

Preprint

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Introduction: Tramadol (TRA) is an opioid analgesic widely prescribed for moderate to severe pain; however, its chronic use is associated with kidney damage. Objectives: This study aimed to assess the impacts of high intensity interval training (HIIT) on the male rat's kidney following chronic TRA administration. Methods: In this experimental study, 30 male Wistar rats were assigned to the following groups: CON; animals received normal saline five days a week in the first month and three days a week second month, EXE; animals conducted (HIIT) according to exercise protocol five days a week for two months, TRA; animals received tramadol 50 mg/kg (i.p.) as described for the CON group. TRA-EXE; animals received tramadol and conducted exercise protocol, and EXE-SL; animals received normal saline and conducted exercise protocol. Then serum malondialdehyde (MDA), total antioxidant capacity (TAC), Glutathione peroxidase (GPx), superoxide dismutase (SOD), albumin (ALB), urea, creatinine (CR), and tissue level of TNFα, IL-6, IL-10 with pathological changes in kidney were measured. P < 0.05 was considered significant using Graph-pad Prism v.9. Results: Exercise in TRA-EXE group increased significantly IL-10, IL-6, MDA, urea, and CR levels compared with TRA group (but not compared to CON). As well, SOD, TAC, GPx, and ALB levels were decreased significantly in TRA-EXE compared with TRA group (but not compared to CON). Pathological findings showed increased inflammatory effect of HIIT even in EXE-TRA due to severe hyperemia seen in all exercise groups. Other findings were in line with the above results. Conclusion: The results showed that HIIT was able to reverse most of harmful effects of tramadol on kidney, including tramadol-induced apoptosis, oxidative stress, and kidney function indices. However, HIIT may lead to increased inflammation, unlike chronic use of tramadol which appeared to ameliorate inflammation. Finally, HIIT might be proposed as a therapeutic strategy for chronic users of tramadol.

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“…6-Dehydrogingerdione has been reported to have anti-inflammatory, antiallergic, antitumor and anti-atherosclerotic properties. 31 Paradol is a potent anticancer, chemopreventive, and anti-inflammatory compound. 32,33 Zingiberene is an established anticancer and antiinflammatory compound.…”

Section: Resultsmentioning

confidence: 99%

Immunomodulatory and Antiallergic Potentials of the Bioactive Compounds of Ginger

B Lalruatfela,

P B Lalthanpuii,

C Lalrinmawia

et al. 2024

Pharmacogn J.

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Background: Allergy is an ever-increasing immune disorder and is often fatal under certain circumstances. Lack of total curative medication prompts the search for various compounds as the lead molecules. Ginger, Zingiber officinale Roscoe, is a well-established medicinal plant in different traditional practices. Its use as antiallergic or anti-inflammatory agent has been vindicated but the underlying mechanism of action is yet unknown. Method: In this study, we analyzed the phytocompounds characterized from ginger for their binding affinities on cysteinyl leukotriene receptor 1 (CysLTR1) and histamine H1 receptor (H1R) by molecular docking. The molecular interactions were compared against known agonists and antagonists of the two receptors. Results: The data indicate that ginger compounds have high binding affinity for both LTR1 and H1R comparable to those of antiallergic medications. The highest binding affinities were recorded for gingerenone-A (-7.3 kcal/mol) and zingiberol (-7.2 kcal/mol) on LTR1; and gingerenone-A (-8.7 kcal/mol) and α-curcumene (-8.0 kcal/mol) on H1R. Conclusion: In addition to antiallergic activity, molecular predications on the probable biological activities of the ginger compounds show that they can have a variety of medicinal applications including immunomodulatory and anticancer activities.

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10-Dehydrogingerdione Attenuates Tramadol-Induced Nephrotoxicity by Modulating Renal Oxidative Stress, Inflammation and Apoptosis in Experimental Rats: Role of HO-1 Activation and TLR4/NF-κB/ERK Inhibition

Cited by 8 publications

References 33 publications

High-Intensity Interval Training Ameliorates Tramadol-Induced Nephrotoxicity and Oxidative Stress in Experimental Rats

High-Intensity Interval Training Ameliorates Tramadol-Induced Nephrotoxicity and Oxidative Stress in Experimental Rats

High Intensity Interval Training (HIIT) Ameliorates the Tramadol-Induced Nephrotoxicity and Oxidative Stress in Experimental Rats

Immunomodulatory and Antiallergic Potentials of the Bioactive Compounds of Ginger

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