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Evaluating protective and therapeutic effects of alpha-lipoic acid on cisplatin-induced ototoxicity.Cell Death & Disease Aug 2018Cisplatin, a small platinum-containing molecule, is a widely used, highly effective anticancer drug. However, severe side effects have been found in cancer patients...
Cisplatin, a small platinum-containing molecule, is a widely used, highly effective anticancer drug. However, severe side effects have been found in cancer patients treated with cisplatin, including nephrotoxicity, neurotoxicity, and ototoxicity. These cisplatin-induced side effects can have a major impact on patient quality of life, including social development problems in pediatric patients that develop hearing loss. Previous studies have suggested that the major cause of cisplatin-induced ototoxicity is abnormal accumulation of reactive oxygen species (ROS) and oxidative stress. Alpha-lipoic acid (ALA), one of the most effective antioxidants, is known to be involved in the cellular antioxidant system and may have a protective effect on cisplatin-induced ototoxicity. However, the therapeutic effect of ALA on damaged hearing function and its detailed mechanism of action are not fully understood. This study focused on determining whether ALA has a potential as a protective and/or therapeutic agent for cisplatin-induced ototoxicity. Histological and physiological analyses were performed using cisplatin-treated mouse cochlea and HEI-OC1 culture cells in pre- and post-treatment with ALA in vitro and in vivo. We found that ALA contributes to protecting mitochondrial function by preventing ROS accumulation and inhibiting apoptotic cell death. Importantly, post-treatment with ALA consistently showed an almost equal restorative effect to pretreatment, in vitro and in vivo, supporting the possible use of ALA as a therapeutic agent for cisplatin-induced ototoxicity. This study is the first report on a strong therapeutic potential of ALA to rescue ototoxic hearing loss caused by cisplatin, and our data provide key evidence that ALA may act as a reducing agent for glutathione disulfide to increase glutathione levels on behalf of glutathione reductase. This result was consistent in both cultured cells and the mouse model, which improves the clinical value of ALA for therapy of cisplatin-induced ototoxicity.
Topics: Animals; Antineoplastic Agents; Apoptosis; Cell Line; Cell Survival; Cisplatin; Ear, Inner; Female; G1 Phase Cell Cycle Checkpoints; Hair Cells, Auditory; Hearing Loss; Male; Mice; Protective Agents; Proto-Oncogene Proteins c-bcl-2; Reactive Oxygen Species; Spiral Ganglion; Stria Vascularis; Thioctic Acid; bcl-2-Associated X Protein
PubMed: 30068942
DOI: 10.1038/s41419-018-0888-z -
Oxidative Medicine and Cellular... 2016Nonalcoholic fatty liver disease (NAFLD) is a spectrum of liver lesions ranging from hepatic steatosis, nonalcoholic steatohepatitis, hepatic cirrhosis, and... (Review)
Review
Nonalcoholic fatty liver disease (NAFLD) is a spectrum of liver lesions ranging from hepatic steatosis, nonalcoholic steatohepatitis, hepatic cirrhosis, and hepatocellular carcinoma. The high global prevalence of NAFLD has underlined the important public health implications of this disease. The pathogenesis of NAFLD involves the abnormal accumulation of free fatty acids, oxidative stress, endoplasmic reticulum (ER) stress, and a proinflammatory state in the liver. Schisandrin B (Sch B), an active dibenzooctadiene lignan isolated from the fruit of (a traditional Chinese herb), was found to possess antihyperlipidemic, antioxidant, anti-ER stress, and anti-inflammatory activities in cultured hepatocytes and in rodent livers . Whereas a long-term, low dose regimen of Sch B induces an antihyperlipidemic response in obese mice fed a high fat diet, a single bolus high dose of Sch B increases serum/hepatic lipid levels in mice. This differential action of Sch B is likely related to a dose/time-dependent biphasic response on lipid metabolism in mice. The hepatoprotection afforded by Sch B against oxidative stress, ER stress, and inflammation has been widely reported. The ensemble of results suggests that Sch B may offer potential as a therapeutic agent for NAFLD. The optimal dose and duration of Sch B treatment need to be established in order to ensure maximal efficacy and safety when used in humans.
Topics: Animals; Cyclooctanes; Humans; Lignans; Models, Biological; Non-alcoholic Fatty Liver Disease; Polycyclic Compounds; Protective Agents
PubMed: 27847552
DOI: 10.1155/2016/6171658 -
International Journal of Molecular... Mar 2019Chemotherapy and/or head and neck radiotherapy are frequently associated with oral mucositis. Oral pain, odynophagia and dysphagia, opioid use, weight loss, dehydration,... (Review)
Review
Chemotherapy and/or head and neck radiotherapy are frequently associated with oral mucositis. Oral pain, odynophagia and dysphagia, opioid use, weight loss, dehydration, systemic infection, hospitalization and introduction of a feeding tube should be mentioned as the main determinated effect of oral mucositis. Oral mucositis leads to a decreased quality of life and an increase in treatment costs. Moreover, oral mucositis is a life-threatening disease. In addition to its own direct life-threatening consequences, it can also lead to a reduced survival due to the discontinuation or dose reduction of anti-neoplasm therapy. There are numerous strategies for the prevention or treatment of oral mucositis; however, their effectiveness is limited and does not correspond to expectations. This review is focused on the ghrelin and obestatin as potentially useful candidates for the prevention and treatment of chemo- or/and radiotherapy-induced oral mucositis.
Topics: Anti-Inflammatory Agents; Gastrointestinal Hormones; Ghrelin; Humans; Mouth Mucosa; Protective Agents; Stomatitis
PubMed: 30934722
DOI: 10.3390/ijms20071534 -
IET Nanobiotechnology 2024This study followed the PRISMA reporting guidelines to present the results. A comprehensive search was performed on electronic databases such as PubMed, Scopus, Web of... (Review)
Review
MATERIALS AND METHODS
This study followed the PRISMA reporting guidelines to present the results. A comprehensive search was performed on electronic databases such as PubMed, Scopus, Web of Sciences, and Science Direct. Initially, 413 articles were retrieved. After removing duplicates and applying specific inclusion and exclusion criteria, 10 articles were finally included in this systematic review.
RESULTS
The reviewed studies showed that selenium nanoparticles had anti-inflammatory and antioxidant properties. They effectively protected the kidneys, liver, and testicles from damage. Furthermore, there was evidence of efficient radioprotection for the organs examined without significant side effects.
CONCLUSIONS
This systematic review emphasizes the potential advantages of using selenium nanoparticles to prevent the negative effects of ionizing radiation. Importantly, these protective effects were achieved without causing noticeable side effects. These findings suggest the potential role of selenium nanoparticles as radioprotective agents, offering possible therapeutic applications to reduce the risks related to ionizing radiation exposure in medical imaging and radiotherapy procedures.
Topics: Selenium; Radiation-Protective Agents; Animals; Humans; Antioxidants; Nanoparticles; Metal Nanoparticles; Radiation Injuries
PubMed: 38863968
DOI: 10.1049/2024/5538107 -
Pharmacology 2021Our liver has a variety of vital functions including removing poisons, storing energy, immunological roles, and secretory and excretory functions. It may face some kinds... (Review)
Review
BACKGROUND
Our liver has a variety of vital functions including removing poisons, storing energy, immunological roles, and secretory and excretory functions. It may face some kinds of diseases caused by viruses, hepatotoxic chemicals, drugs, alcohol, and inherited disorders. Oxidative stress and inflammation are in the core of mechanisms of liver damages induced by viruses or chemical agents.
SUMMARY
Morus nigra (M. nigra), generally known as black mulberry, exhibited wide-spectrum pharmacological effects including antidiabetic, antinociceptive, anticancer, and hepatoprotective activities. Different parts of this plant particularly the fruit and leaf have shown beneficial effects on hepatocytes in cell culture and animal models of liver damages induced by chemicals (e.g., CCl4), drugs (e.g., paracetamol), diet (e.g., high fat), diabetes, etc. The beneficial effects of M. nigra on the liver are attributed to the presence of considerable amounts of phenolic compounds such as anthocyanins, flavonols, and phenolic acids. The present review is aimed to focus on the hepatoprotective activities of M. nigra and its phytochemicals and the mechanisms responsible for these activities. Key Messages: The evidence reviewed in this study can help design clinical trials on M. nigra in patients with liver disorders and develop a hepatoprotective herbal medicine.
Topics: Animals; Humans; Liver; Liver Diseases; Morus; Phenols; Phytochemicals; Plant Extracts; Protective Agents
PubMed: 33849010
DOI: 10.1159/000515032 -
Journal of Ayub Medical College,... 2018Humans are exposed either deliberately or unintentionally to a variety of diverse chemicals that harm the kidney. To reduce the alarming high incidence of...
BACKGROUND
Humans are exposed either deliberately or unintentionally to a variety of diverse chemicals that harm the kidney. To reduce the alarming high incidence of nephrotoxicity, some chemical as well as herbal alternatives are needed. Nimesulide belongs to a group of antiinflammatory drugs that are in common use in our society. Like all non-steroidal antiinflammatory drugs, it carries a potential threat of nephrotoxicity especially when other risk factors are present in user. The objective of this study was to find herbal alternative with antiinflammatory and nephroprotective qualities and to bring into light its mechanism of nephroprotection.
METHODS
This experimental study was conducted on mice at National Institute of Health, Islamabad from Feb 2013 to March 2014. Nimesulide was given in a dosage of 750 mg/kg body weight for 3 days to induce nephrotoxicity and protective effect of Picrorhiza kurroa was noted in two doses of 250 mg/kg and 500 mg/kg for 14 days. Renal function tests were done and urinary PGE2 was measured to assess the effect of nimesulide and Pk on kidneys.
RESULTS
In our study, significant improvement was seen in serum urea and creatinine levels in mice receiving low and high dose Picrorhiza kurroa. However, no significant improvement was noted in urinary PGE2 showing that the mechanism of nephroprotection is not by vasodilatory effect of Pk.
CONCLUSIONS
This study showed nimesulide nephrotoxic potential and Pk is a good herbal antiinflammatory and nephroprotective alternative for nimesulide but its mechanism of nephroprotection is not by PGE2.
Topics: Animals; Kidney; Kidney Diseases; Kidney Function Tests; Mice; Picrorhiza; Plant Extracts; Protective Agents; Sulfonamides
PubMed: 29938416
DOI: No ID Found -
Biomedicine & Pharmacotherapy =... Nov 2022Chemotherapy is one of the causes of ovarian injury and infertility. Although assisted reproductive technology helps young female patients with cancer become pregnant,... (Review)
Review
BACKGROUND
Chemotherapy is one of the causes of ovarian injury and infertility. Although assisted reproductive technology helps young female patients with cancer become pregnant, preventing chemotherapy-induced ovarian injury will often possess even more significant benefits.
OBJECTIVE
We aimed at demonstrating the hazardous effects and mechanisms of ovarian injury by chemotherapeutic agents, as well as demonstrating agents that protect the ovary from chemotherapy-induced injury.
RESULTS
Chemotherapeutic agents cause death or accelerate activation of follicles and damage to the blood vessels in the ovary, resulting in inflammation. These often require drug development to protect the ovaries from injury.
CONCLUSIONS
Our findings provide a basis for the development of drugs to protect the ovaries from injury. Although there are many preclinical studies on potential protective drugs, there is still an urgent need for a large number of clinical experiments to verify their potential use.
Topics: Pregnancy; Humans; Female; Ovarian Follicle; Antineoplastic Agents; Ovarian Diseases; Protective Agents
PubMed: 36179491
DOI: 10.1016/j.biopha.2022.113731 -
Anais Da Academia Brasileira de Ciencias May 2017The endothelium is fundamental for the regulation of vascular tone and structure. Under disease conditions, including the presence of cardiovascular disease risk... (Review)
Review
The endothelium is fundamental for the regulation of vascular tone and structure. Under disease conditions, including the presence of cardiovascular disease risk factors, the endothelium loses its protective role and becomes a proatherosclerotic structure. In this article we searched for strategies from PUBMED and Science Direct databases using the following key words: endothelium, natural bioactive compounds, polyphenols and cardiovascular diseases. The search was restricted to english language papers. Studies have identified the contribution of diet to the risk of developing cardiovascular diseases. In this context, high intakes of fruit and vegetables are associated with the decrease of cardiovascular diseases. Thus the most important fruit/vegetables and bioactive compounds to prevent endothelial diseases are berries, apples, virgin olive oil, tomatoes, soybeans, and polyphenols, carotenoids and unsaturated fatty acids, respectively. The bioactive compounds from fruit and vegetables provide endothelial protection through the following mechanisms: improved eNOS/NO bioavailability, attenuates oxidative stress, inhibited NF-κB pathway and decreased cell adhesion molecules expression. In this article natural bioactive compound mechanisms of endothelium protection are thoroughly reviewed.
Topics: Diet, Mediterranean; Endothelium, Vascular; Fruit; Humans; Protective Agents; Vegetables
PubMed: 28538813
DOI: 10.1590/0001-3765201720160509 -
Journal of Cellular and Molecular... Sep 2021Excitotoxic events underlying ischaemic and traumatic brain injuries activate degenerative and protective pathways, particularly in the hippocampus. To understand...
Excitotoxic events underlying ischaemic and traumatic brain injuries activate degenerative and protective pathways, particularly in the hippocampus. To understand opposing pathways that determine the brain's response to excitotoxicity, we used hippocampal explants, thereby eliminating systemic variables during a precise protocol of excitatory stimulation. N-methyl-d-aspartate (NMDA) was applied for 20 min and total RNA isolated one and 24 h later for neurobiology-specific microarrays. Distinct groups of genes exhibited early vs. delayed induction, with 63 genes exclusively reduced 24-h post-insult. Egr-1 and NOR-1 displayed biphasic transcriptional modulation: early induction followed by delayed suppression. Opposing events of NMDA-induced genes linked to pathogenesis and cell survival constituted the early expression signature. Delayed degenerative indicators (up-regulated pathogenic genes, down-regulated pro-survival genes) and opposing compensatory responses (down-regulated pathogenic genes, up-regulated pro-survival genes) generated networks with temporal gene profiles mirroring coexpression network clustering. We then used the expression profiles to test whether NF-κB, a potent transcription factor implicated in both degenerative and protective pathways, is involved in the opposing responses. The NF-κB inhibitor MG-132 indeed altered NMDA-mediated transcriptional changes, revealing components of opposing expression signatures that converge on the single response element. Overall, this study identified counteracting avenues among the distinct responses to excitotoxicity, thereby suggesting multi-target treatment strategies and implications for predictive medicine.
Topics: Animals; Brain Injuries, Traumatic; Gene Expression Regulation; Hippocampus; N-Methylaspartate; NF-kappa B; Protective Agents; Rats; Rats, Sprague-Dawley
PubMed: 34414662
DOI: 10.1111/jcmm.16864 -
Ulusal Travma Ve Acil Cerrahi Dergisi =... Jul 2020The hypothesis of our study is that sugammadex has protective efficacy against ischemia-reperfusion (I/R) injury in rats.
BACKGROUND
The hypothesis of our study is that sugammadex has protective efficacy against ischemia-reperfusion (I/R) injury in rats.
METHODS
Our study included 28 male Wistar Albino rats. The rats were assigned to four groups. The sham group had no procedure other than anesthesia administration. The control group received three hours of ischemia and 24 hours of reperfusion. The Sgdx4 group received 4 mg/kg, and the Sgdx16 group received 16 mg/kg sugammadex intravenously, and then, reperfusion was applied. Histopathological investigation, and serum creatine kinase (CK), lactate dehydrogenase (LDH), and serum and tissue malondialdehyde (MDA) and superoxide dismutase (SOD) analyses were performed.
RESULTS
When the sham group and the control group were compared, there were statistically significant differences histopathologically (p<0.01). There was no significant difference between the Sgdx4 group compared with the sham and control groups histopathologically (p>0.01). There was a significant difference between the Sgdx16 group and the sham group histopathologically (p<0.01). There were significant differences between the sham and control groups concerning CK and LDH levels (p<0.01). There was a significant difference in the levels of CK between the control group and Sgdx4 group and in the levels of CK and LDH between the control group and Sgdx16 group (p<0.01).
CONCLUSION
In our study, we examined the histological and biochemical protective effects of 4 mg/kg sugammadex on unilateral lower extremity I/R injury in rats. The findings suggest that a 4 mg/kg dose of sugammadex was more effective than a 16 mg/kg dose.
Topics: Animals; Disease Models, Animal; Lower Extremity; Male; Protective Agents; Rats; Rats, Wistar; Reperfusion Injury; Sugammadex
PubMed: 32589239
DOI: 10.14744/tjtes.2019.12524