Mycotoxins from Tomato Pathogenic Alternaria alternata and Their Combined Cytotoxic Effects on Human Cell Lines and Male Albino Rats

Abstract

The Alternaria species is considered to contain a plethora of several mycotoxins constituting a risk factor for both human and animal health. This work aimed mainly to explore the cytotoxicity of a combined mixture of altenuene (ALT), alternariol (AOH), tenuazonic acid (TeA), and altenuisol (AS) toxins produced by pathogenic A. alternata toward human oral epithelial cells (PCS-200-014), lung fibroblast cells (WI-38), and male albino rats. The sequencing of the multi-locus, RNA polymerase second largest subunit (rpb2), glyceraldehyde-3-phosphate dehydrogenase (gapdh), and Alternaria major allergen gene (Alt a 1) was performed to infer relationships among isolated Alternaria species. The phylogenetic analysis of gapdh, rpb2, and Alt-a 1 sequence data indicated that all isolates resided in A. alternata. The pathogenic potentiality of A. alternata was investigated on tomato plants cv. super strain B under greenhouse conditions, and all isolates were pathogenic to tomato plants, with significant (p < 0.05) variations. The ability of A. alternata isolates to produce mycotoxins was also explored using high-performance liquid chromatography (HPLC). All tested isolates were able to produce at least one of the assessed mycotoxins—ALT, AOH, TeA, and AS—and ALT was reported as the dominant mycotoxin, produced by 80% of A. alternata isolates. The cytotoxic properties of the combined mixture of ALT, AOH, TeA, and AS at concentrations of 31.25, 62.50, 125, 250, and 500 µg/mL were assessed via the MTT assay method after exposure for 24 h versus the control. The treatment of both cell lines with combined mixtures of ALT, AOH, TeA, and AS showed a dose-dependent decrease in cell viability. The highest concentrations tested at 62.50, 125, 250, and 500 µg/mL significantly decreased cell viability and caused cell damage compared to the lowest concentration of 31.25 µg/mL and the control. The cytotoxicity and genotoxicity of the combined mixtures of ALT, AOH, TeA, and AS on male albino rats were also investigated via the gene expression of (TNF-α) and using hematological (CBC), chemical (alanine aminotransferase (ALT), aspartate aminotransferase (AST) and urea and creatinine), and histopathological analyses. A marked increase was observed in the levels of ALT, AST, urea and creatinine, TNF-α gene expression, red blood cells (RBCs), white blood cells (WBCs), hemoglobin (Hb), and packed cell volume % (PCV) after 28 days of exposure relative to the untreated control. Pathological alterations were also observed in the liver and kidney tissues of rats. Conclusively, this work provides a new understanding on the cytotoxicity and genotoxicity of mycotoxins of pathogenic A. alternata from tomatoes.

Fungal and mycotoxin contaminants in cannabis and hemp flowers: implications for consumer health and directions for further research

“…For example, Penicillium and Aspergillus are members of the same family, yet they only have a few secondary metabolites in common ( Samson et al, 2011 ), and their mycotoxin profiles are very different from other members of the cannabis floral mycobiome. Other fungi such as Alternaria, Cladosporium, Chaetomium, Mucor, and Trichoderma that can be found in cannabis inflorescences ( Table 1 ) may also produce different cytotoxic and genotoxic mycotoxins such as PAT, alternariol, tenuazonic acid ( Ismail et al, 2023 ), chaetoglobosins ( Fogle et al, 2008 ), viridin, and gliotoxin ( Sugui et al, 2007 ; Bulgari et al, 2020 ) when adequate fungal growth has been achieved. This list is not exhaustive but is reflective of the diversity of the floral mycobiome from a few recent studies ( Punja et al, 2023 ).…”

Fusarium Species Responsible for Tomato Diseases and Mycotoxin Contamination and Biocontrol Opportunities

“…For example, FUM B1 is genotoxic and a cancer promoter, while ZEN is an estrogenic mycotoxin, being linked with endometrial adenocarcinoma and hyperplasia [21,91]. Also, in an essay with rats, DON-induced DNA damage and the expression of proteins related to inflammatory response implied the apoptotic pathway [92].…”