Paraquat (PQ) is a toxic, organic herbicide for which there is no specific antidote. Although banned in some countries, it is still used as an irreplaceable weed killer in others. The lack of understanding of the precise mechanism of its toxicity has hindered the development of treatments for PQ exposure. While toxicity is thought to be related to PQ-induced oxidative stress, antioxidants are limited in their ability to ameliorate the untoward biological responses to this agent. Summarized in this review are data on the absorption, distribution, metabolism, excretion, and toxicity (ADME/T) of PQ, focusing on the essential roles of individual transporters and enzymes in these processes. Based on these findings, strategies are proposed to design and test specific and effective antidotes for the clinical management of PQ poisoning.

Aluminum phosphide (ALP) poisoning is a true medical emergency associated with high mortality. The lack of a specific antidote for ALP poisoning mandates searching for new treatment modalities. This study aimed to evaluate the effectiveness and safety of gastric decontamination by paraffin oil in cases with acute ALP poisoning. This study was a randomized, controlled, parallel-group, single-blind, phase II clinical trial conducted over a period of 6 months. Sixty-two patients with acute ALP poisoning were randomly allocated into two equivalent groups. In both groups, the standard ALP treatment was given. Gastric decontamination in the control group was performed by saline and sodium bicarbonate 8.4%, while in the intervention group, it was done by paraffin oil and sodium bicarbonate 8.4%. All patients were subjected to history taking, clinical examination, and laboratory investigations. The outcomes were evaluated. The median age of the studied patients was 20 years. Most of the studied cases were females, single, and from rural areas. The median delay time was 1 h. All patients included in the study alleged ingestion of ALP during suicidal attempts. Twelve hours after admission, many clinical and laboratory findings were significantly better in the intervention group. The need for intubation, mechanical ventilation, and total amount of vasopressors was significantly lower, and the mortality rate was non-significantly lower in the intervention group compared to the control. The median length of hospital stay was significantly shorter in the control group. Gastric decontamination with paraffin oil and sodium bicarbonate 8.4% could be valuable in reducing ALP poisoning severity, the need for intubation, mechanical ventilation, and vasopressors.

During the past decade, nanotechnologies opened a new era in delivery of plant protection products through the development of nanosized controlled release systems, such as polymer nanoparticles, micelles, and so on using a wide variety of materials. To increase the pesticides penetration into the grain under the presowing seed treatment, a new approach based on non-covalent associate preparation with natural polysaccharides and oligosaccharides as delivery systems (DSs) was applied. Earlier, this approach was tested on antidote 1,8-naphthalic anhydride (NA). Enhancement of the NA solubility and penetration into the barley and wheat seeds had been demonstrated. In the present study, these DSs were used to prepare nanocomposites of pesticides (tebuconazole, imidacloprid, imazalil, prochloraz). The composite formation of the pesticides with poly- and oligosaccharides was proved by NMR relaxation method. Enhancement of the pesticides solubility and improvement of its penetration into the seeds of corn and rapeseeds has been detected. The strongest enhancement of penetration ability was observed for arabinogalactan nanocomposites: 5-folds for tebuconazole and imidacloprid, and more than 10-folds for imazalil and prochloraz. Our data show that the effect of polysaccharides and oligosaccharides on the nanopesticide penetration might be associated with the solubility enhancement, affinity of DSs to the surface of grains, and the modification of cell membranes by poly- and oligosaccharides.

Quantum dots (QDs) have caused large challenges in clinical tests and biomedical applications due to their potential toxicity from nanosize effects and heavy metal components. In this study, the physiological responses of Phanerochaete chrysosporium (P. chrysosporium) to CdSe/ZnS QDs with either an inorganic sulfide NaHS or an organic sulfide cysteine as antidote have been investigated. Scanning electron microscope analysis showed that the hyphal structure and morphology of P. chrysosporium have obviously changed after exposure to 100 nM of COOH CdSe/ZnS 505, NH₂ CdSe/ZnS 505, NH₂ CdSe/ZnS 565, or NH₂ CdSe/ZnS 625. Fourier transform infrared spectroscopy analysis indicated that the existence of hydroxyl, amino, and carboxyl groups on cell surface could possibly conduct the stabilization of QDs in an aqueous medium. However, after NaHS or cysteine treatment, the cell viability of P. chrysosporium exposed to CdSe/ZnS QDs increased as compared to control group, since NaHS and cysteine have assisted P. chrysosporium to alleviate oxidative damage by regulating lipid peroxidation and superoxide production. Meanwhile, NaHS and cysteine have also stimulated P. chrysosporium to produce more antioxidant enzymes (superoxide dismutase and catalase), which played significant roles in the defense system. In addition, NaHS and cysteine were used by P. chrysosporium as sulfide sources to promote the glutathione biosynthesis to relieve CdSe/ZnS QDs-induced oxidative stress. This work revealed that sulfide sources (NaHS and cysteine) exerted a strong positive effect in P. chrysosporium against the toxicity induced by CdSe/ZnS QDs.

In this study, we present experimental data on the effects of meso-2,3-dimercaptosuccinic acid (DMSA) and tetraethylammonium salt of salinomycinic acid (Sal) on cadmium-induced spleen dysfunction and altered essential metal balance in mice. Sixty-day-old male mice (ICR line) were randomly divided into four groups: untreated control group (Ctrl)—obtained distilled water for 28 days, toxic control group (Cd)—exposed to cadmium acetate dihydrate at average daily dose of 20mg/kg body weight (BW) for 14 days, Cd + DMSA group—obtained cadmium acetate dihydrate as the toxic control group followed by treatment with 20mg/kg BW DMSA for 2 weeks, and Cd + Sal group—mice exposed to cadmium acetate dihydrate at average daily dose of 20mg/kg BW for 2 weeks followed by administration of Sal at an average daily dose of 20mg/kg BW for 2 weeks. The compounds were administered orally via the drinking water of the animals. We found that cadmium exposure caused splenomegaly and reduced the hemoglobin and hematocrit levels and total red blood cell count compared with untreated controls. Cadmium intoxication of mice induced accumulation of the toxic metal ion in the blood and spleen. Alterations in the endogenous levels of calcium (Ca) and iron (Fe) in the spleen of cadmium-exposed mice compared with those in untreated controls were observed. Treatment of cadmium-exposed mice with DMSA or Sal recovered the spleen weight and hematological parameters to normal control values, decreased cadmium concentration in the blood and spleen, and improved splenic architecture. The results prove that Sal is a potential antidote for treatment of Cd-induced spleen dysfunction.

Dimethoate is a widely used organophosphate insecticide known to be toxic to the pancreas. The aim of this study is to detect the possible protective effects of the fenugreek seed ethanolic extract on the biochemical, histological, and ultra-structural abnormalities induced by dimethoate chronic exposure in the pancreas of adult male rats. The study was conducted on 50 adult male albino rats that were divided equally into 5 groups: (group I) negative control, (group II) vehicle control group, (group III) fenugreek-treated group that was given 400 mg/kg ethanolic fenugreek seed extract once daily, (group IV) dimethoate group received 20 mg/kg/day dimethoate, and (group V) dimethoate- + fenugreek-treated group received a combination of dimethoate and fenugreek in the same previous doses. Dimethoate treatment caused a significant increase in serum glucose, amylase, and lipase levels and a significant decrease in serum insulin. A significant increase in lipid peroxidation and pro-fibrotic cytokine (TGF-β1) together with a significant reduction of the antioxidant {reduced glutathione (GSH), catalase (CAT), superoxide dismutase (SOD)} activities and the anti-inflammatory (IL-4) in pancreatic tissues was also recorded. There was a histological and ultra-structural evidence of pancreatic acinar and islet cell injury. The recorded abnormalities were reversed in dimethoate+fenugreek treated group indicating that fenugreek ethanolic extract can serve as an antidote for dimethoate-induced pancreatic insult.

Methylmercury (MeHg) is a highly toxic environmental pollutant which binds with a high affinity to selenol groups. In view of this, seleno-compounds have been investigated as MeHg antidotes. In the present study, we evaluated the effects of the co-exposure to MeHg and the seleno-compound diphenyl diselenide (PhSe)₂ on Drosophila melanogaster. We measured the survival rate, developmental survival, locomotor ability, reactive oxygen species (ROS) production, and Hg levels in D. melanogaster exposed to MeHg and/or (PhSe)₂ in the food. Exposure to MeHg caused a reduction in the survival rate, developmental survival, and locomotion in D. melanogaster. In addition, MeHg increased the ROS production and mercury levels in flies. The co-exposure to MeHg and (PhSe)₂ did not prevent the toxic effects of MeHg in D. melanogaster. On the contrary, the co-exposure enhanced the toxic effects on the locomotor ability and developmental survival. This effect may be explained by the fact that the co-exposure increased the Hg levels in body when compared to flies exposed only to MeHg, suggesting that MeHg and (PhSe)₂ interaction may increase Hg body burden in D. melanogaster which could contribute for the increased toxicity observed in the co-exposure.

The global burden of heavy metal especially mercury, arsenic, lead, and cadmium toxicities remains a significant public health challenge. Developing nations are particularly at high risk and carry the highest burden of this hazard. Chelation therapy has been the mainstay for treatment of heavy metal poisoning where the chelating agent binds metal ions to form complex ring–like structures called “chelates” to enhance their elimination from the body. Metal chelators have some drawbacks such as redistribution of some heavy metals from other tissues to the brain thereby increasing its neurotoxicity, causing loss of essential metals such as copper and zinc as well as some serious adverse effects, e.g., hepatotoxicity. The use of natural antidotes, which are easily available, affordable, and with little or no side effects compared to the classic metal chelators, is the focus of this review and suggested as cheaper options for developing nations in the treatment of heavy metal poisoning.