Purpose
Renal failure is an end-stage consequence after persistent hyperglycemia during diabetic nephropathy (DN), and the etiology of DN has been linked to oxidative stress. The purpose of this ...research was to determine the beneficial synergistic effects of S-Allyl Cysteine (SAC) and Taurine (TAU) on oxidative damage in the kidneys of type 2 diabetic rats induced by hyperglycemia.
Design/methodology/approach
Experimental diabetes was developed by administering intraperitoneal single dose of streptozotocin (STZ; 65 mg/kg) with nicotinamide (NA; 230 mg/kg) in adult rats. Diabetic and control rats were treated with SAC (150 mg/kg), TAU (200 mg/kg) or SAC and TAU combination (75 + 100 mg/kg) for four weeks. The estimation of body weight, fasting blood glucose (FBG), oral glucose tolerance test (OGTT), oxidative stress markers along with kidney histopathology was done to investigate the antidiabetic potential of SAC/TAU in the NA/STZ diabetic group.
Findings
The following results were obtained for the therapeutic efficacy of SAC/TAU: decrease in blood glucose level, decreased level of thiobarbituric acid reactive substances (TBARS) and increased levels of GSH, glutathione-s-transferase (GST) and catalase (CAT). SAC/TAU significantly modulated diabetes-induced histological changes in the kidney of rats.
Originality/value
SAC/TAU combination therapy modulated the oxidative stress markers in the kidney in diabetic rat model and also prevented oxidative damage as observed through histopathological findings.
Although the precise mechanisms contributing to secondary brain injury following traumatic brain injury are complex and obscure, a number of studies have demonstrated that inflammatory responses are ...an obvious and early feature in the pathogenesis of traumatic brain injury. Inflammasomes are multiprotein complexes that prompt the stimulation of caspase-1 and subsequently induce the maturation and secretion of proinflammatory cytokines, such as interleukin-1β and interleukin-18. These cytokines play a pivotal role in facilitating innate immune responses and inflammation. Among various inflammasome complexes, the NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome is the best characterized, a crucial role for NLRP3 has been demonstrated in various brain diseases, including traumatic brain injury. Several recent studies have revealed the contribution of NLRP3 inflammasome in identifying cellular damage and stimulating inflammatory responses to aseptic tissue injury after traumatic brain injury. Even more important, blocking or inhibiting the activation of the NLRP3 inflammasome may have substantial potential to salvage tissue damage during traumatic brain injury. In this review, we summarize recently described mechanisms that are involved in the activation and regulation of the NLRP3 inflammasome. Moreover, we review the recent investigations on the contribution of the NLRP3 inflammasome in the pathophysiology of TBI, and current advances and challenges in potential NLRP3-targeted therapies. A significant contribution of NLRP3 inflammasome activation to traumatic brain injury implies that therapeutic approaches focused on targeting specific inflammasome components could significantly improve the traumatic brain injury outcomes.
Diabetes mellitus (DM) and steroid medication, coincided with coronavirus disease 2019 (COVID-19), results in a weakened immune system, allowing some commonly found pathogens to become more harmful. ...Mucormycosis (black fungus) is a type of opportunistic infection caused by fungi belonging to the Mucorales family. DM is the most prominent risk factor for mucormycosis. Excessive blood sugar and decreased insulin levels lead to diabetic ketoacidosis (DKA), a devastating complication of DM that can be fatal if left untreated.
Diabetic ketoacidosis is more common in type 1 diabetic patients, although it can also be fall in type 2 diabetic patients. DKA occurs when the body lacks enough insulin to allow blood sugar to enter the cells and is used for energy. Instead, the liver breaks down fat for fuel-producing chemicals known as ketones.
When too many ketones are created too quickly, they can reach dangerously high levels in the body. Mucormycosis is a rare but serious infectious disease that requires medication or surgical removal.
The confluence of diabetes and COVID-19 makes managing mucormycosis a serious and dead issue. Although the effectiveness of prophylactic antifungal therapy has yet to be demonstrated, hyperglycemia control appears to be the most important step in managing mucormycosis in DKA patients.
Abstract The present study was designed to evaluate the beneficial synergistic effects of S-allyl Cysteine (SAC) and Taurine (TAU) on hyperglycemia, lipid profile and renal damage markers in type 2 ...diabetes mellitus (T2DM) in rats. Experimental T2DM was developed by administering an intraperitoneal single dose of nicotinamide (NA; 230 mg/kg) and streptozotocin (STZ; 65 mg/ kg) in adult rats. Control and diabetic rats were treated with SAC (150 mg/kg); TAU (200 mg/ kg) or SAC and TAU (75+100 mg/kg) combination for four weeks. Measurements of traditional markers of kidney toxicity in serum, such as blood urea nitrogen (BUN), serum creatinine (Scr), and alkaline phosphatase (ALP), together with serum cholesterol/triglyceride such as serum total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and very low-density lipoprotein cholesterol (VLDL-C) may yield a snapshot of renal damage and lipid profile in NA/STZ-treated rats. The variation in levels of fasting blood glucose, glycosylated hemoglobin, insulin and lipid profile was significantly augmented in SAC/TAU treatment group. The diabetic group showed elevated renal injury markers in serum, which were decreased significantly by SAC/TAU treatment. Thus the results of the experiment clearly indicate the potential of the SAC/TAU combination in improving diabetic complications.
Synergistic strategy is always supported by nature due to multi-targets synergistic mode. Spices are one of the most nutritional products present in our diet, and dietary manipulation has been ...implicated in managing various medical conditions. Our interest was to study the effect of polyherbal formulation (PHF), composed of fenugreek, black seed, cumin, and flaxseed, in the experimental model of diabetic nephropathy (DN). After induction of diabetes (streptozotocin 55 mg/kg) in male Wistar rats, PHF (200 mg/kg) was given for 56 days. Biochemical and histopathological indicators were used to study nephritis. The diabetic group had elevated glucose, dyslipidemia, and impaired renal function. PHF treatment improved glycemic control, renal function, and dyslipidemia. Consecutively, oxidative damage marked as the elevated level of 8-hydroxy-2′-deoxyguanosine (8-OHdG), transforming growth factor-beta1 (TGF-β1) and malonaldehyde (MDA) with concomitantly decreased glutathione (GSH), glutathione reductase (GR) and superoxide dismutase (SOD) depicted in the diabetic group were restored after the administration of PHF. Further histological analysis was done and explored as glomerulosclerosis and interstitial fibrosis in the diabetic group. Administration of PHF significantly modulated renal histological variations in diabetic rats. A current investigation concluded that PHF exhibited a strong nephroprotective effect by preserving renal damage due to its antidiabetic and antioxidant actions. Thus, PHF may find a pharmaceutical candidature to manage diabetes-related complications requiring more studies.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Diabetes mellitus (DM) is among the most frequently reported comorbidities in patients tainted with the pandemic coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome ...coronavirus 2 (SARS-CoV-2). With a high pervasiveness of diabetes mellitus, there is an urgency to understand the special aspects of COVID-19 in hyperglycemic patients. Diabetic patients are at higher risk than the general population of viral or bacterial infections, thus require special attention since diabetes is linked with severe, critical, and lethal modes of COVID-19.
The objective of this study was to focus on epidemiology, pathophysiology, mechanism, and management of DM with COVID-19.
The search was carried out on databases portals such as Pubmed, EMBASE, Google Scholar, and CINAHL with the keywords, i.e., COVID-19, coronavirus, SARS-CoV-2, diabetes, covid-19, etc. Result: DM and COVID-19 disease conditions can impact each other in terms of clinical progression and outcome. Available laboratory/clinical observations suggest that hyperglycemia-induced immune dysfunction, inflated lactate grades, and cytokines storm may play critical roles in the seriousness of COVID-19 in patients with diabetes; however, the exact mechanisms linking diabetes and COVID-19 remain to be further clarified.
Standards to constrain the disease spread at the individual and community level are the key to extenuate the speedily rising pandemic, while definitive treatment, like plasma therapy, chemoprophylaxis, or vaccine for COVID-19, has yet to be discovered.
The study was designed to search the efficacy of the oil blend, composed of sesame, canola, walnut, and wheat germ oils against diabetic nephropathy (DN). In the present study, the notion that a ...vegetable oil blend (VOB) minimizes oxidative damage, reduces renal injury, and preserves renal architecture was tested. Male wistar rats received VOB (2 ml/ kg−1) for 56 days after diabetes induction (streptozotocin 55 mg kg−1). Biochemical evidences in serum and renal tissue had been used to evaluate the impact on kidney injury and supported with histopathological examination. A significant increase in blood glucose, blood urea nitrogen (BUN), N-acetyl-β-D-glucosaminidase (NAG), and proteinuria levels with a concomitant decrease in glomerular filtration rate (GFR) were noted in diabetic rats. Oxidative damage indices such as 8-hydroxy-2′-deoxyguanosine (8-OHdG), transforming growth factor-beta1 (TGF-β1), malonaldehyde (MDA) and glutathione (GSH) were found higher in diabetic group with diminished glutathione reductase (GR) and superoxide dismutase (SOD) antioxidant enzymes level. Histological examination also revealed significant alterations, including glomerulosclerosis and interstitial fibrosis in diabetic group. Administration of VOB significantly modulated abnormalities in markers of renal dysfunction and tubular damage. Further oxidative damage and renal histological changes were recovered in the treatment group. In conclusion, our findings strongly suggest that renoprotective effect of VOB on nephrotic damage is attributable to its potential antidiabetic and antioxidant capabilities. There is still work to be done on a longer-term investigation or a clinical trial.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Industrial and occupational exposure to chromium compounds, particularly hexavalent chromium (Cr(VI))-containing compounds are often known to cause acute renal injury (ARI) in humans and animals. Its ...nephrotoxicity is associated with an increased formation of reactive oxygen species and lipid peroxidation in renal tissue. Recent studies suggest that antioxidants of the vitamin E family have protective effects against metal toxicity. Tocotrienols are known to have greater antioxidant activity than tocopherols and protect more efficiently against some free radical-related diseases than does tocopherols. In the present study, ARI induced by potassium dichromate (K
2Cr
2O
7) has been used as a model to investigate the possible nephroprotective effect of tocotrienol-rich fraction (TRF) from palm oil. Wistar male rats having an average body weight (bw) of 210
g were divided into four groups. The first group was taken as control and injected with vehicle alone while the second group was drug control and ingested with TRF (200
mg/kg, bw, orally, once daily for 21 days); the third group served as toxicant and was pre-treated with saline, followed by a single subcutaneous (SC) injection of K
2Cr
2O
7 (15
mg/kg bw). The fourth group was pre-treated with TRF and subsequently injected with K
2Cr
2O
7 (same dose as for the third group). Renal functions, oxidative and nitrosative stress were evaluated on days 0, 1, 2, 4, 7, 11 and 14 after treatment with K
2Cr
2O
7. The results revealed altered proximal tubular function; decreased glomerular filtration accompanied by oxidative damage 48
h after exposure to dichromate; while in the TRF-treated group proximal reabsorptive function, glomerular function and the cellular redox status were sustained. These results were further supported and confirmed by histological findings. The study suggests that TRF is effective in preventing K
2Cr
2O
7-induced acute renal injury, but more studies are needed to confirm the effects of TRF as a nephroprotective agent.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
A number of experimental and clinical findings have consistently demonstrated the protective effects of Pycnogenol® (PYC) in the management of diabetes. However, the protective mechanism by which PYC ...provides protection in a model type I diabetes has not been studied. This study examines the beneficial effect of PYC on hyperglycemia, inflammatory markers, and oxidative damage in diabetic rats. We also evaluated the possible mechanism of action of PYC which might be that it stimulates beta islet expression, which has been implicated in the process of insulin secretion and diabetes management. Diabetes was induced in rats by an intraperitoneal injection of streptozotocin (STZ; 60 mg/kg body weight) followed by free access to 5 % glucose for the next 24 h. Four days after STZ injection, rats were supplemented with PYC (10 mg/kg body weight) for 4 weeks. At the end of the experiment, blood was drawn, and rats were then sacrificed, and their livers and pancreases were dissected for biochemical and histological assays. The level of fasting blood glucose and glycosylated hemoglobin significantly increased but amylase, insulin, and hepatic glycogen level decreased in the STZ group. PYC significantly augmented these effects in STZ + PYC group. The STZ group showed elevated level of nitric oxide, tumor necrosis factor-α, and interleukin-1beta in serum which were decreased by PYC treatment. Moreover, PYC significantly ameliorated increased thiobarbituric reactive substances, protein carbonyl, and decreased levels of glutathione, glutathione-s-transferase, and catalase activity in the liver and pancreas of the STZ rats. Histopathological and immunohistochemical examination also revealed a remarkable protective effect of PYC. The study suggests that PYC is effective in reducing diabetic-related complications in a type I model of diabetes and might be beneficial for the treatment of diabetic patients.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, VSZLJ, ZAGLJ
Ischemic stroke is one of the major causes of morbidity and mortality worldwide. Mitochondria play a vital role in the pathological processes of cerebral ischemic injury, but its transplantation and ...underlying mechanisms remain unclear. In the present study, we examined the effects of mitochondrial therapy on the modulation of AMPK and SIRT1/PGC-1α signaling pathway, oxidative stress, and NLRP3 inflammasome activation after photothrombotic ischemic stroke (pt-MCAO). The adult male mice were subjected to the pt-MCAO in which the proximal-middle cerebral artery was exposed with a 532-nm laser beam for 4 min by retro-orbital injection of a photosensitive dye (Rose Bengal: 15 mg/kg) before the laser light exposure and isolated mitochondria (100 μg protein) were administered intranasally at 30 min, 24 h, and 48 h following post-stroke. After 72 h, mice were tested for neurobehavioral outcomes and euthanized for infarct volume, brain edema, and molecular analysis. First, we found that mitochondria therapy significantly decreased brain infarct volume and brain edema, improved neurological dysfunction, attenuated ischemic stroke-induced oxidative stress, and neuroinflammation. Second, mitochondria treatment inhibited NLRP3 inflammasome activation. Finally, mitochondria therapy accelerated p-AMPKα(Thr172) and PGC-1α expression and resorted SIRT1 protein expression levels in pt-MCAO mice. In conclusion, our results demonstrate that mitochondria therapy exerts neuroprotective effects by inhibiting oxidative damage and inflammation, mainly dependent on the heightening activation of the AMPK and SIRT1/PGC-1α signaling pathway. Thus, intranasal delivery of mitochondria might be considered a new therapeutic strategy for ischemic stroke treatment.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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