Journal of Current Toxicology and Venomics - Volume 4, Issue 1, 2024

The detection of microcystins in blood, respiratory mucosa, and urine samples to diagnose acute or chronic microcystin intoxication is difficult and requires sophisticated analysis techniques. Finding simple and quick methods to assess the exposure of individuals to microcystins is crucial.

This study aims to assess the presence of specific antibodies (IgG, IgE, IgA, and IgM) against microcystin-LR in individuals exposed to cyanobacterial blooms as a non-complex biomarker.

Blood samples were taken to reveal the presence of specific antibodies as well as to measure a standard set of biochemical parameters. All volunteers were administered a questionnaire regarding their water usage, health status, and habits. Significant differences in the antibody content were studied between exposed and non-exposed people to cyanobacterial blooms.

We found that out of 73 studied individuals, 87.7% of them showed positive results for at least one of the four types of antibodies tested. The prevalent isotype was IgE, and significant differences were detected for all isotypes between the exposed and non-exposed groups. The biochemical profile was altered in some cases.

The presence of specific antibodies in serum could be used as exposure biomarkers to complement epidemiological studies and medical diagnosis of microcystin intoxications. The in-house ELISA method, developed by our group for the detection of antibodies, should now be improved in terms of specificity and accuracy. These findings also indicate that more research should be conducted on the protective role and duration of antibodies.

Acetaminophen overdose is a leading cause of acute liver failure globally. Current treatment options, primarily N-acetylcysteine (NAC), have limitations. Mito-TEMPO (Mito-T), a mitochondria-targeted antioxidant, has shown potential in preclinical studies. This systematic review evaluated the evidence for Mito-T's hepatoprotective effects against acetaminophen-induced liver injury.

We conducted a comprehensive search of databases and grey literature following PRISMA guidelines. Studies published between 2000 and 2023 on Mito-T and acetaminophen-induced hepatotoxicity in animal models were included. Data on study characteristics, interventions, outcomes, and risk of bias were extracted.

Six high-quality studies were included. Mito-T administration significantly reduced serum alanine transaminase (ALT) levels, a marker of liver injury, compared to controls. Mito-T also protects against hepatocellular necrosis, apoptosis, and mitochondrial dysfunction. These effects were likely mediated by Mito-T's ability to scavenge reactive oxygen and nitrogen species within mitochondria.

This review provides strong evidence that Mito-T effectively protects against acetaminophen-induced liver injury in animal models. Mito-T’s mechanisms of action address a critical pathophysiological pathway in acetaminophen toxicity. While limitations, including the use of animal models and potential for publication bias, exist, the findings suggest Mito-T holds promise as a novel therapeutic option. Further studies are needed to assess Mito-T's safety, pharmacokinetics, and optimal dosing in humans. Clinical trials comparing Mito-T against NAC are warranted if toxicity profiles are favorable. Additionally, investigating Mito-T's potential in other diseases involving oxidative stress is crucial.

Spices, including Amomum subulatum and Coriander sativum, are not only popular for improving food flavour but are also accepted worldwide for their health benefits in various disorders.

This study aimed to elucidate the possible mechanism for the anti-apoptotic effect of terpene-rich extract of Amomum subulatum and Coriandrum sativum against the rodent model of cardiotoxicity.

Effects of standardized terpenoids-rich aqueous methanolic extract of two commonly used spices, viz. Amomum subulatum Roxb. and Coriandrum sativum Linn., were investigated on doxorubicin-induced apoptotic changes and cardiotoxicity in Wistar rats with the aim of investigating the mechanism. Prior to the in vivo experiment, the extracts were subjected to quantitative estimation of possible bioactive markers of the terpenes by employing a newly developed, optimized, and validated GC-MS method along with TLC profiling.

Cardiotoxicity was evident from elevated creatinine kinase (CK-MB), lactate dehydrogenase (LDH), and malondialdehyde (MDA) levels in the toxic control group after treatment with doxorubicin (2.5 mg/kg i.p. given twice a week for three weeks). Caspase-3, Tumor necrosis factor-α (TNF-α), and Interleukin-6 (IL-6) were also induced in animals treated with doxorubicin. Treatment with Amomum subulatum and Coriandrum sativum at the doses of 100 and 200 mg/kg exhibited significant (P<0.001) reversal of CK-MB, LDH, MDA, Caspase-3, TNF-α, and IL-6 levels. This protective effect was further supported by the results of DNA gel electrophoresis and histopathological observations.

This study supports the cardioprotective role of selected spices against doxorubicin-induced cardiotoxicity through the anti-apoptotic mechanism.

Some neurotoxins inhibit nerves strongly. Saxitoxins and tetrodotoxin exhibit strong affinity for various voltage-gated sodium channels (VGSCs), including Nav 1.7, but low affinity for Nav 1.8. Emerging data suggests AGAP mediate analgesia by binding voltage-independently to sodium channel site-3.

This study examined AGAP's mechanism and analgesic efficacy during sciatic nerve block.

In rats, partial sciatic nerve ligation caused rapid and persistent mechanical hyperalgesia. Mechanical hyperalgesia after medication delivery was assessed with von Frey filaments. Western blot and immunohistochemical staining assessed VGSC expression following drug treatment.

The data showed that lidocaine and AGAP increased paw withdrawal threshold compared to control rats. Compared to the control group, lidocaine or AGAP inhibited VGSCs.

This study suggested that AGAP inhibits VGSCs to elicit lidocaine-like analgesia.

More than 80% of the world's population uses herbal remedies in some form. Heavy metal contamination and the attendant health risks of Indian herbal medicines are not adequately documented.

This study aimed to investigate the health risks associated with four common heavy metal contaminants, namely lead, arsenic, cadmium, and mercury, present in raw medicinal herbs cultivated or growing wild in the West Bengal state of India.

A total of 197 raw herbs obtained from herbal medicine practitioners or wild plant collectors from 16 districts spread across 3 geographical zones (south, central, north) of West Bengal were analyzed. In accordance with AOAC specifications, all samples were dried in a hot air oven, ground into a coarse powder, and then processed and analyzed for heavy metals through atomic absorption spectrometry. The mean concentrations were estimated along with standard deviations, overall, zone-wise, and according to the botanical part tested. The standardized human health risk indices were calculated from the results.

Significant amounts of heavy metals were found in the herb samples analyzed in the order: lead in 150 samples (76.1%), arsenic in 84 (42.6%), cadmium in 77 (39%), and mercury in 47 (23.8%). Central zone samples had the highest concentrations of lead (10.06 µg/g), arsenic (0.62 µg/g), and cadmium (0.54 µg/g), while the greatest amount of mercury (0.08 µg/g) was obtained in herbs from South zone. There were also considerable variations with respect to the source of the botanical part. Lead and cadmium concentrations showed a significant positive correlation (r = 0.588). Although risk assessment using standardized measures indicated some risk, the human Hazard Index (HI) was less than 1 for all metals, indicating that it was mostly safe to use the herbs in the short-term. However, the risk of health issues from prolonged use still remains.

Significant contaminations were identified, but exposure would mostly be within acceptable risk levels at present. However, since risk would be cumulative over time, programs need to be in place to monitor pharmaceutical herb safety, identify local sources of pollution, and take appropriate remedial action.

Crotalus durissus cumanensis (C.d.c.) is the most widely distributed snake in Venezuela, causing the majority of snakebite envenoming.

The purpose of this study was to produce IgY antibodies against a C.d.c. venom pool from different Venezuelan regions and evaluate their neutralization capacity on various venom toxic activities.

Anti-C.d.c. venom antibodies are purified from chicken egg yolks by precipitation with polyethylene glycol and further analyzed by Multiple Antigen Blot Assay, indirect ELISA, Western blot, and Inhibition assays. In addition, we evaluate the phospholipase, edematogenic, and hemorrhagic activities. In addition, a new envenoming simulation study using anti-C.d.c. venom IgY in mice is presented.

In this study, we show that anti-C.d.c. venom IgY is capable of neutralizing 4 LD50 doses of the Cdc venom (i.e., 1.76 mg of IgY neutralized 14 µg of C.d.c. venom) and effectively neutralizing the phospholipase, edematogenic and hemorrhagic activities. Additionally, the anti C.d.c. venom IgY specifically recognizes polypeptide bands with apparent molecular masses of ~ 54.55, 30.39, 24.1, 14.02, and 9.44 kDa by western blot. The IgY specificity is demonstrated by a dose-dependent inhibition, in which antibodies pre-adsorbed with the C.d.c. venom does not recognize the proteins contained in the venom. Furthermore, in the simulation study of envenoming, the mice inoculated with IgY showed no response.

Our results support the use of anti-venom IgY as an alternative to traditional equine therapy in animals and, eventually, in human patients bitten by C.d.c snakes.

In India and other tropical nations, snake bites are a serious public health issue that anti-snake venom may effectively treat.

The case report described here details the antivenom received to neutralize the toxins present in Russell’s viper venom, followed by Ayurveda treatment to remove the surgical wound and reduce joint stiffness by applying Ayurvedic paste prepared by Laportea aestuans (L.). The leaves, garlic, pepper, and lemon juice mixture was applied to the affected area twice daily for 10 days. Another thin paste consisting of Laportea aestuans (L.) leaves, Centella asiatica (L.), garlic, pepper, and lemon juice was applied every 30 minutes for 10 days. A dried medicated paste was prepared by heating coconut oil and dried neem tree peel and applied to the wound. The patient was also given a decoction of Randia dumetorum (Retz.) Poir nut extracted with milk to flush out the venom.

The present results suggest combining conventional allopathic treatment to heal the surgical wound and Ayurvedic treatments to manage the symptoms of a juvenile Russell's viper bite as effective.

Envenomation with Odontobuthus doriae scorpion results in pain at the bite site, inflammation, necrosis, and neurotoxicity. Administration of anti-scorpion antiserum prepared from immunized horses is the main therapy for envenomation. However, in some cases, anaphylactic shock related to antiserum administration limits its use. Therefore, the identification of the venom component and the development of a specific neutralizing agent is very important. Identification of linear epitopes of O. doriae using a peptide-displayed phage library (Ph.D.TM -7) was the main aim of the current study.

Three rounds of biopanning were performed on immobilized immunoglobulins (IgGs) isolated from the sera of an immunized horse. The biopanning process was checked by polyclonal phage enzyme-linked immunosorbent assay (ELISA). Forty blue phage colonies were randomly selected from the third round of biopanning, amplified, DNA extracted and submitted for sequencing.

Polyclonal phage ELISA results confirmed the progress of the biopanning process. The antigens involved in stimulating the horse's immune system were identified, namely sodium channel toxin, potassium channel toxin, chloride channel toxin, cell protein, venom protein, and antimicrobial peptide.

Identified epitopes promise further research to develop novel diagnostic or therapies against O. doriae envenomation.

Spiders are predators that use their venom to immobilize their prey. These spider toxins are able to affect the central nervous system of mammals.

We hypothesized that venom from the tarantula Vitalius platyomma may induce behavioral changes in male Wistar rats. To test this hypothesis, the behavioral effects of venom were investigated after intracerebroventricular microinjection using the neuroethological method (behavioral sequences) associated with the ETHOMATIC program, evaluating frequency, duration, and strength of statistical association between pairs (dyads) of behaviors.

The results obtained in this present study showed that the intracerebral administration of V. platyomma crude venom provoked a difference in the time of freezing of animals. In addition, animals showed after the freezing period changes in the exploratory and grooming clusters and additional complex sequences of behaviors such as wild running.

This study clearly demonstrated the appearance of seizure-like behaviors, similar to audiogenic brainstem-dependent seizures such as those observed in genetically-selected audiogenic strains.

Venom allergens have been identified in the venom of scorpion, snake, bee, wasp, etc. Some allergy reactions in humans may refer to the venom allergens.

Phylogenetic analysis of venom allergens from the transcriptome of Hemiscorpius lepturus scorpion was the main aim of the study.

Seven venom allergens: HLAllergen1, HLAllergen2, HLAllergen3, HLAllergen4, HLAllergen5, HLAllergen6, and HLAllergen7 have been identified in the venom of Hemiscorpius lepturus scorpion using venom gland transcriptome analysis. Primary, secondary and tertiary structures of the identified venom allergens were predicted using ExPASy ProtParam, PSIPRED, and SWISS MODEL servers. Phylogenetic tree was constructed using MEGA 11 software through neighbor-joining method with 1000 bootstraps.

Structure analysis of identified venom allergens showed a molecular weight of between 46 to 52 kDa. Tertiary structure results showed that all predicted 3-D structures were in a normal range. Phylogenetic tree analysis showed that HLAllergen 3, 4 and 5 were formed single clades and HLAllergen 1, 2, 7, and 6 other clades.

However, further studies using proteomic analysis of H. lepturus are needed to confirm and compare with transcriptome data.

Snakebites are a worldwide health problem and produce pathological symptoms, such as hemorrhage, tissue necrosis, blood coagulation disorder, edema, and death. Although serum therapy protects victims from death, it does not prevent amputation of the affected limb. Therefore, alternative treatments deserve attention.

To test a new series of twelve disubstituted triazoles, TRI 02, TRI 03, TRI 04, TRI 05, TRI 07, TRI 08, TRI 09, TRI 11, TRI 14, TRI 16, TRI 17, and TRI 18 against the hemorrhagic, edematogenic, hemolytic, coagulant, and proteolytic activities of Lachesis muta muta venom.

The derivatives were incubated with L. muta venom (incubation protocol), then the toxic activities were measured. L. m. muta venom was injected before (treatment protocol) or after (prevention protocol) the derivatives.

Most of the derivatives inhibited the proteolytic and hemolytic activity of L. m. muta venom, but only TRI 17 inhibited coagulation activity. The derivatives TRI 03, TRI 05, TRI 07, TRI 14, and TRI 17 inhibited hemorrhage, while TRI 07, TRI 08, and TRI 16 inhibited edema. The derivatives TRI 03, TRI 07, and TRI 11 inhibited hemorrhage whether they were administered before or after L. m. muta venom. According to in silico tool, TRI 03, TRI 04, TRI 07, TRI 08, TRI 09, TRI 16, TRI 17, and TRI 18 were not toxic. The derivatives did not violate Lipinksi’s rule of five.

These triazoles serve as molecules able to improve the treatment of L. m. muta envenoming.