Melatonin increased antioxidant capacity to ameliorate growth retardation and intestinal epithelial barrier dysfunction in diquat-challenged piglets.

BACKGROUND: Diquat is a common environmental pollutant, which can cause oxidative stress in humans and animals. Diquat exposure causes growth retardation and intestinal damage. Therefore, this study was performed to investigate the effects of melatonin on diquat-challenged piglets. RESULTS: Dietary supplementation with 2 mg kg-1 melatonin significantly increased the average daily gain and feed conversion rate in piglets. Melatonin increased antioxidant capacity, and improved intestinal epithelial barrier function of duodenum and jejunum in piglets. Moreover, melatonin was found to regulated the expression of immune and antioxidant-related genes. Melatonin also alleviated diquat-induced growth retardation and anorexia in diquat-challenged piglets. It also increased antioxidant capacity, and ameliorated diquat-induced intestinal epithelial barrier injury. Melatonin also regulated the expression of MnSOD and immuner-elated genes in intestinal. CONCLUSION: Dietary supplementation with 2 mg kg-1 melatonin increased antioxidant capacity to ameliorate diquat-induced oxidative stress, alleviate intestinal epithelial barrier injury, and increase growth performance in weaned piglets. © 2023 Society of Chemical Industry.

Magnolol supplementation alleviates diquat-induced oxidative stress via PI3K-Akt in broiler chickens.

This experiment was conducted to investigate the effects of magnolol on the oxidative parameters and jejunum injury induced by diquat in broiler chickens. This test adopts a 2 × 2 factors design, a total of 288 one-day-old male AA broiler chicks randomly allocated to four groups, consisting of six replicates of 12 birds each, which was then denoted as CON group, diquat (DIQ) group (16 mg/kg BW diquat was injected into birds at the age of 21 days), magnolol (MAG) group (basic bird diet supplemented with 300 mg/kg magnolol), and MAG + DIQ group. At 21 days of age, broilers in the DIQ group and the MAG + DIQ group were intraperitoneally injected with 16 mg/kg BW diquat. Results showed that diet supplementing with MAG could alleviate the decrease of ADG to a certain extent after exposure to DIQ. Addition of magnolol to the diet alleviated the decrease of ADG during injection, antioxidant enzymes, and gene expression and increased the markers of oxidative damage induced by diquat induction. Magnolol supplement reversed the increase of apoptotic cells in the diquat-induced chicken jejunum. RNA sequencing showed that PI3K-Akt, calcium, and NF-kappa B signaling pathways were the main enrichment pathways between the DIQ group and the MAG + DIQ group. Our findings revealed that magnolol may improve antioxidant enzyme activity and expression of related genes through the PI3K-Akt pathway to alleviate oxidative stress.

A Case of a Lethal Diquat Ingestion in a Toddler.

BACKGROUND: Diquat is an herbicide that may cause rapid and profound systemic toxicity. It can cause multisystem organ failure, primarily via its effects on the gastrointestinal, renal, cardiovascular, and central nervous systems. Case fatality rates as high as 43% have been reported. There is a paucity of pediatric literature on diquat poisoning, and in this article, we will discuss an unfortunate pediatric case that highlights the severity of diquat toxicity. CASE REPORT: We present the case of a child who ingested diquat, which led to multisystem organ failure and death. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Clinicians should be aware of this herbicide's potential for significant morbidity and mortality, especially in children, in whom small quantities can be lethal. It is important that emergency physicians are aware of the significant toxicity of diquat and provide early gastric decontamination, as it is the only proven therapeutic strategy.

circGLI3 Inhibits Oxidative Stress by Regulating the miR-339-5p/VEGFA Axis in IPEC-J2 Cells.

As a new type of noncoding RNA, circular RNA (circRNA) is stable in cells and not easily degraded. This type of RNA can also competitively bind miRNAs to regulate the expression of their target genes. The role of circRNA in the mechanism of intestinal oxidative stress (OS) in weaned piglets is still unclear. In our research, diquat (DQ) was used to induce OS in small intestinal epithelial cells (IPEC-J2) to construct an OS cell model. Mechanistically, dual luciferase reporter assays, fluorescence in situ hybridization (FISH), and western blotting were performed to confirm that circGLI3 directly sponged miR-339-5p and regulated the expression of VEGFA. Overexpression of circGLI3 promoted IPEC-J2 cell proliferation, increased the proportion of S-phase cells (P < 0.01), and reduced reactive oxygen species (ROS) generation when IPEC-J2 cells were subjected to OS. circGLI3 can increase the activity of glutathione peroxidase (GSH-Px) and the total antioxidant capacity (T-AOC) in IPEC-J2 cells and reduce the malondialdehyde (MDA) content and levels of inflammatory factors. Therefore, overexpression of circGLI3 reduced oxidative damage, whereas miR-339-5p mimic counteracted these effects. We identified a regulatory network composed of circGLI3, miR-339-5p, and VEGFA and verified that circGLI3 regulates VEGFA by directly binding miR-339-5p. The expression of VEGFA affects IPEC-J2 cell proliferation, cell cycle progression, and ROS content and changes the levels of antioxidant enzymes and inflammatory factors. This study reveals the molecular mechanism by which circGLI3 inhibits OS in the intestine of piglets and provides a theoretical basis for further research on the effect of OS on intestinal function.

Pterostilbene as a protective antioxidant attenuates diquat-induced liver injury and oxidative stress in 21-day-old broiler chickens.

This study investigated the effects of pterostilbene (PT) supplementation on growth performance, hepatic injury, and antioxidant variables in a broiler chicken model with diquat (DQ)-induced oxidative stress. There were 192 one-day-old male Ross 308 broiler chicks randomly allocated to one of two treatment groups: 1) broilers fed a basal diet and 2) broilers fed a diet supplemented with 400 mg/kg PT. At 20 D of age, half of the broilers in each group were intraperitoneally injected with DQ (20 mg per kg BW), whereas the other half were injected with an equivalent amount of sterile saline. Diquat induced a rapid loss of BW (P < 0.001) 24 h post-injection, but dietary PT supplementation improved the BW change of broilers (P = 0.014). Compared with unchallenged controls, the livers of DQ-treated broilers were in severe cellular damage and oxidative stress, with the presence of higher plasma transaminase activities (P < 0.05), a greater number of apoptotic hepatocytes (P < 0.001), and an increased malondialdehyde content (P = 0.007). Pterostilbene supplementation prevented the increases in plasma aspartate aminotransferase activity (P = 0.001), the percentage of hepatocyte apoptosis (P < 0.001), and the hepatic malondialdehyde accumulation (P = 0.011) of the DQ-treated broilers. Regarding the hepatic antioxidant function, PT significantly increased total antioxidant capacity (P = 0.007), superoxide dismutase activity (P = 0.016), reduced glutathione content (P = 0.011), and the ratio of reduced glutathione to oxidized glutathione (P = 0.003), whereas it reduced the concentration of oxidized glutathione (P = 0.017). Pterostilbene also boosted the expression levels of nuclear factor erythroid 2-related factor 2 (P = 0.010), heme oxygenase 1 (P = 0.037), superoxide dismutase 1 (P = 0.014), and the glutamate-cysteine ligase catalytic subunit (P = 0.001), irrespective of DQ challenge. In addition, PT alleviated DQ-induced adenosine triphosphate depletion (P = 0.010). In conclusion, PT attenuates DQ-induced hepatic injury and oxidative stress of broilers presumably by restoring hepatic antioxidant function.

Dietary Tributyrin Attenuates Intestinal Inflammation, Enhances Mitochondrial Function, and Induces Mitophagy in Piglets Challenged with Diquat.

The study evaluated the effects of butyric acid, in the form of tributyrin on the oxidative stress, inflammation, and mitochondrial function in diquat-challenged pigs. Twenty-four weaned pigs were allocated to four treatments in a 2 × 2 factorial arrangement with the main effects of tributyrin supplementation and diquat challenge. The results showed that supplemental tributyrin increased ( P < 0.05) average daily gain and average daily feed intake of diquat-challenged pigs. Tributyrin elevated ( P < 0.05) the activities of total antioxidant capacity and superoxide dismutase, reduced ( P < 0.05) malondialdehyde content, and increased ( P < 0.05) mRNA levels of copper and zinc superoxide dismutase and manganese-containing superoxide dismutase of diquat-challenged pigs. Tributyrin relieved ( P < 0.05) intestinal inflammation reflected by decreased mRNA abundances of tumor necrosis factor-α, interferon-γ, and interleukin-6 in the intestine. Tributyrin reduced ( P < 0.05) serum diamine oxidase activity and d-lactate content, increased ( P < 0.05) transepithelial electrical resistance, decreased paracellular flux of dextran (4 kDa), and prevented the diquat-induced decrease ( P < 0.05) in the expressions of claudin-1, occludin, and zonula occludens-1. Tributyrin alleviated ( P < 0.05) diquat-induced mitochondrial dysfunction shown by lowered reactive oxygen species, increased mitochondrial membrane potential, and increased adenosine triphosphate content. Furthermore, tributyrin increased ( P < 0.05) expressions of mitophagy proteins (PTEN-induced putative kinase 1 and Parkin), and ratio of light chain 3-II to light chain 3-I in intestine. Collectively, tributyrin attenuated oxidative stress and intestinal inflammation, improved mitochondrial function, and induced mitophagy in diquat-challenged pigs.

Arginine metabolism and its protective effects on intestinal health and functions in weaned piglets under oxidative stress induced by diquat.

The intestine plays key roles in maintaining body arginine (Arg) homoeostasis. Meanwhile, the intestine is very susceptible to reactive oxygen species. In light of this, the study aimed to explore the effects of Arg supplementation on intestinal morphology, Arg transporters and metabolism, and the potential protective mechanism of Arg supplementation in piglets under oxidative stress. A total of thirty-six weaned piglets were randomly allocated to six groups with six replicates and fed a base diet (0·95 % Arg,) or base diet supplemented with 0·8 % and 1·6 % l-Arg for 1 week, respectively. Subsequently, a challenge test was conducted by intraperitoneal injection of diquat, an initiator of radical production, or sterile saline. The whole trial lasted 11 d. The diquat challenge significantly decreased plasma Arg concentration at 6 h after injection (P<0·05), lowered villus height in the jejunum and ileum (P<0·05) as well as villus width and crypt depth in the duodenum, jejunum and ileum (P<0·05). Oxidative stress significantly increased cationic amino acid transporter (CAT)-1, CAT-2 and CAT-3, mRNA levels (P<0·05), decreased arginase II (ARGII) and inducible nitric oxide synthase mRNA levels, and increased TNF- α mRNA level in the jejunum (P<0·05). Supplementation with Arg significantly decreased crypt depth (P<0·05), suppressed CAT-1 mRNA expression induced by diquat (P<0·05), increased ARGII and endothelial nitric oxide synthase mRNA levels (P<0·05), and effectively relieved the TNF- α mRNA expression induced by diquat in the jejunum (P<0·05). It is concluded that oxidative stress decreased Arg bioavailability and increased expression of inflammatory cytokines in the jejunum, and that Arg supplementation has beneficial effects in the jejunum through regulation of the metabolism of Arg and suppression of inflammatory cytokine expression in piglets.

Oxidative stress affects sperm performance and ejaculate redox status in subordinate house sparrows.

Oxidative stress is the result of random cellular damage caused by reactive oxygen species that leads to cell death, ageing or illness. Most physiological processes can result in oxidative stress, which in turn has been identified as a major cause of infertility. In promiscuous species, the fertilizing ability of the ejaculate partly determines the male reproductive success. When dominance determines access to fertile females, theory predicts that lower ranking males should increase resource investment into enhancing ejaculate quality. We hypothesized that subordinate males should thus prioritize antioxidant protection of their ejaculates to protect them from oxidative stress. We put this hypothesis to the test by chronically dosing wild house sparrows with diquat (∼1 mg kg-1), a herbicide that increases pro-oxidant generation. We found that, although they increased their antioxidant levels in the ejaculate, diquat-treated males produced sperm with reduced velocity. Importantly, and contrary to our hypothesis, males at the bottom of the hierarchy suffered the largest reduction in sperm velocity. We suggest that resource access hinders individuals' ability to cope with environmental hazards. Our results point at oxidative stress as a likely physiological mechanism mediating ejaculate quality, while individual ability to access resources may play a role in constraining the extent to which such resources can be allocated into the ejaculate.

Ratios of biliary glutathione disulfide (GSSG) to glutathione (GSH): a potential index to screen drug-induced hepatic oxidative stress in rats and mice.

Hepatotoxicity of drug candidates is one of the major concerns in drug screening in early drug discovery. Detection of hepatic oxidative stress can be an early indicator of hepatotoxicity and benefits drug selection. The glutathione (GSH) and glutathione disulfide (GSSG) pair, as one of the major intracellular redox regulating couples, plays an important role in protecting cells from oxidative stress that is caused by imbalance between prooxidants and antioxidants. The quantitative determination of the GSSG/GSH ratios and the concentrations of GSH and GSSG have been used to indicate oxidative stress in cells and tissues. In this study, we tested the possibility of using the biliary GSSG/GSH ratios as a biomarker to reflect hepatic oxidative stress and drug toxicity. Four compounds that are known to alter GSH and GSSG levels were tested in this study. Diquat (diquat dibromide monohydrate) and acetaminophen were administered to rats. Paraquat and tert-butyl hydroperoxide were administered to mice to induce changes of biliary GSH and GSSG. The biliary GSH and GSSG were quantified using calibration curves prepared with artificial bile to account for any bile matrix effect in the LC-MS analysis and to avoid the interference of endogenous GSH and GSSG. With four examples (in rats and mice) of drug-induced changes in the kinetics of the biliary GSSG/GSH ratios, this study showed the potential for developing an exposure response index based on biliary GSSG/GSH ratios for predicting hepatic oxidative stress.

Nail injury and diquat exposure: forgotten but not gone.

Primary fingernail changes that result from chemical exposures are seldom encountered in clinical practice. A cluster investigation was conducted on employees at a pesticide packaging company. Six employees reported simultaneous onset of defects occurring in their fingernails, including nail discoloration, nail dimpling, and nail shedding. Multiple pesticides and herbicides including diquat were used in the facility at the time of the cluster onset. A literature review noted 6 articles published before 1975 documenting similar nail changes associated with paraquat, diquat, or other herbicide use. Only one such case report published after 1985 could be located. Diquat was the only material that was previously reported in the medical literature as causing nail defects and also in use at this facility. Diquat exposure is the most plausible explanation for the observed changes in these workers' fingernails.

Oral mucosal response to exposure to diquat: a rare occupational injury.

Diquat is a quaternary ammonium herbicide closely related to paraquat, and is used commonly by commercial and domestic gardeners. The systemic toxicity of this group of compounds is well-known, but isolated human oral mucosal responses to topical exposure are not well-reported. We present details of an accidental mucosal exposure to diquat during manufacture and the resultant injury, and give guidance for appropriate management of such an exposure.

Melatonin reduces mortality and oxidatively mediated hepatic and renal damage due to diquat treatment.

The bipyridyl herbicide, diquat, is a potent prooxidant that generates superoxide anions through redox cycling in vivo. Exposure to elevated levels of this compound causes acute hepatic and renal toxicity as well as death in rodents. In the present study, we investigated whether melatonin, a free radical scavenger and antioxidant, could protect against diquat-induced hepatic and renal damage and whether the indole would improve survival of Kunming mice given a lethal dose of diquat. When mice were intraperitoneally (i.p.) given a single dose of diquat (50 mg/kg body weight), liver and kidney injuries were observed at 6 hr as indicated by elevated serum levels of both alanine aminotransferase (ALT) activity and blood urea nitrogen (BUN). In addition, lipid peroxidation levels in both liver and kidney showed significant increases as shown by elevated concentrations of F(2)-isoprostanes. The administration of melatonin (20 mg/kg) 30 min before the diquat injection resulted in a significant reduction in serum levels of ALT and BUN as well as hepatic and renal F(2)-isoprostanes levels. For the survival study, 75 mg/kg diquat was administered i.p. into mice to induce acute death. Without melatonin treatment, 10 of 23 (43.5%) mice died within 24 hr after diquat injection. Pretreatment with melatonin (20 mg/kg) 30 min prior to the injection of diquat and thereafter at 4-hr intervals until the end of the observation period (24 hr), reduced the death rate to two of 22 (9.1%) mice. Chi-squared test revealed a significant difference with P < or = 0.05. In conclusion, melatonin, a broad spectrum antioxidant, reduces hepatic and renal damage and lowers the death rate in diquat-treated mice.

Pathways involved in mild gastrointestinal inflammation induced by a low level exposure to a food contaminant.

Chronic gut inflammation is associated with radical oxygen species (ROS) genesis. ROS may activate certain transcription factors such as nuclear factor kappa beta (NF-kappaB), which regulates cyclooxygenase-2 (COX-2). Diquat, a food contaminant, is responsible for oxidative stress. This work aimed to establish the involvement of ROS and prostanoids on diquat-induced gastrointestinal inflammation and mast cell hyperplasia. Diquat increased gastrointestinal MPO activity and mast cell number. Its effect on gastric MPO activity was reversed by PD 138,387 (a COX-2 selective inhibitor) and PDTC (an inhibitor of NF-kappaB activation) but not by DMSO (a hydroxyl radical scavenger) and allopurinol (a xanthine oxidase inhibitor). In contrast, increased jejunal MPO activity was blocked by both DMSO, PD 138,387, and PDTC, while allopurinol enhanced it. PD 138,387 and PDTC reduced gastrointestinal mast cell number while DMSO and allopurinol did not Diquat-induced inflammation involves a gastrointestinal NF-kappaB activation and COX-2 dependent proinflammatory prostanoid synthesis. Furthermore, the hydroxyl radical is involved in intestinal but not gastric inflammation.

Occupational voice disorders due to workplace exposure to irritants--a review of the literature.

The medical literature contains relatively few examples of reports of voice disorders that could be attributed to chemical exposure at work. General medical conditions such as gastro-oesophageal reflux and the use of medication such as inhaled steroids are well-recognized causes of laryngitis, but the occupational causes are less well documented. This paper describes the results of a literature review looking at the reporting of cases of occupationally acquired voice disorders due to exposure to irritants in the workplace.

Mixed diquat/paraquat-induced burns.

BACKGROUND: Ducatalon is a bipyridylium herbicide containing a mixture of diquat and paraquat, and is used in agriculture. Adverse reactions due to contact of this compound with the skin have rarely been described. CASE REPORTS: Two men were seen for severe pain due to extensive chemical burns in the perineal and scrotal regions, caused by leaking of Ducatalon from defective equipment used for spraying the herbicide. The lesions responded well to treatment with topical silver sulfadiazine, combined with systemic antibiotics. The damaged skin healed without scarring within a few days. The lesions have not recurred after the faulty spraying apparatus was replaced. CONCLUSION: Direct contact of the skin with Ducatalon may lead to severe chemical burns. Proper precautions should be taken by the personnel handling this compound, with particular attention to the integrity of the equipment used for spraying the herbicide.

Ocular injury caused by Preeglox-L, a herbicide containing paraquat, diquat and surfactants.

Two patients were splashed in the eye accidentally with an aliquot of Preeglox-L, a herbicide containing paraquat, diquat and surfactants. Despite immediate flushing of the eye with copious amounts of water, in both cases the corneal epithelium deteriorated one to two weeks after the incident. Thereafter, the lesions in each eye healed gradually.

Oxidant stress following renal ischemia: changes in the glutathione redox ratio.

Pretreatment of animals with certain antioxidant enzymes and substances decreases renal damage following ischemia and reperfusion. The hypothesis that reoxygenation imposes an oxidant stress has been used to explain this. The present study has directly assessed oxidant stress under these conditions by measuring the glutathione redox ratio ([GSSG/(GSH + GSSG)] x 100) in freeze-clamped kidney. The glutathione peroxidase system plays a role in removing peroxides which result from oxidant stress, generating GSSG from GSH in the process. The selenium-dependent glutathione peroxidase can metabolize H2O2 and other hydroperoxides. A non-selenium-dependent glutathione peroxidase activity is present and can metabolize organic hydroperoxides, but it cannot metabolize H2O2. Under anesthesia, the left renal artery was occluded for 40 minutes and then reflow was allowed. Kidneys were freeze clamped before reflow and after 5, 10, and 15 minutes of reflow. The contralateral kidney was freeze clamped and used as a control. The control value for the glutathione redox ratio was 1.09 +/- 0.05. This fell during ischemia to 0.67 +/- 0.22 and increased significantly to 1.66 +/- 0.29 after five minutes of reperfusion. By 15 minutes it had returned to 1.09 +/- 0.22. Treatment of rats with diquat, which causes a severe oxidant stress, raised the glutathione redox ratio from 0.88 +/- 0.12 to 1.89 +/- 0.15. Thus, reperfusion was concluded to cause a large but transient oxidant stress. Selenium-deficient rats were used to examine the nature of the oxidant stress. Activity of the selenoenzyme glutathione peroxidase was depressed to 2% of control in the kidneys of these rats.(ABSTRACT TRUNCATED AT 250 WORDS)