The therapeutic outcome of cisplatin is limited due to its adverse side effects in normal tissues. Despite its potent antineoplastic effect, cisplatin is known by a relevant collateral action, for instance, acute renal failure. The aim of this study was to assess the effectiveness of Pituranthos chloranthus (PC) essential oil for contracting cisplatin-induced toxicity, in Balb/c mice. The standard mouse model of cisplatin-induced acute kidney injury (AKI), consisting of one intraperitoneal injection of cisplatin (20&#x2009;mg/kg), was adopted. Mice were pretreated by intraperitoneal administration of PC (5 and 10&#x2009;mg/Kg b.w) for one week. Cisplatin induced alteration in renal and liver functions, evidenced by increased serum biomarkers levels (creatinine, ALT, and AST). Significant mitigation of cisplatin-induced toxicity was confirmed by lowered levels of serum biomarkers and reduced DNA damage in liver and kidney. PC also restored the alterations in oxidative stress markers and proinflammatory cytokine IFN-&#x3b3; level. Overall, this study provides, for the first time, that PC can be applied as an antioxidant-adjuvant treatment to mitigate cisplatin-induced renal failure.

Aida Lahmar

Zaineb Dhaouefi

Rihab Khlifi

Fairouz Sioud

Leila Chekir- Ghedira

Pituranthos chloranthus Oil as an Antioxidant-Based Adjuvant Therapy against Cisplatin-Induced Nephrotoxicity

Contaminations of chemicals in foods and drinks are raising public concerns. Among these, styrene, a monomer for plastic production, receives increasing interest due to its ability to leach from the packaging and contaminate in foods and drinks causing many health problems. The present study was designed to investigate the effects of styrene monomer (STR) and its metabolite styrene oxide (STO) on C2C12 myoblast proliferation and differentiation. Based on an MTT assay, both STR and STO showed no cytotoxic effect at 10&#x2013;100&#x2009;&#x3bc;M. However, at 50&#x2013;100&#x2009;&#x3bc;M STO, but not STR, significantly inhibited cell proliferation. The STO-treated cells were accumulated in S-phase of cell cycles as revealed by flow cytometry. The antioxidant enzyme (catalase and superoxide dismutase) activities and the gene expressing these enzymes of the arrested cells were decreased and ultimately led to nuclear condensation and expression of apoptotic markers such as cleaved caspase-3 and-9, but not cleaved caspase-8. In addition, STO significantly suppressed myogenic differentiation by decreasing both the number and size of differentiated myotubes. Biochemical analysis showed attenuations of total protein synthesis and myosin heavy chain (MHC) protein expression. In conclusion, a metabolite of styrene, STO, leached from plastic packaging of foods and beverages suppressed both myoblast proliferation and differentiation, which would affect skeletal muscle development and regeneration.

Piyaporn Surinlert

Nitchamon Kongthong

Mariam Watthanard

Thannicha Sae-lao

Piyawat Sookbangnop

Chumpol Pholpramool

Chittipong Tipbunjong

Styrene Oxide Caused Cell Cycle Arrest and Abolished Myogenic Differentiation of C2C12 Myoblasts

A battery of OECD- and GLP-compliant toxicological studies was performed to assess the safety of a highly purified germanium sesquioxide, an organic form of the naturally occurring, nonessential trace element germanium. Germanium dioxide and germanium lactate citrate (inorganic germaniums) have been shown to induce renal toxicity, whereas germanium sesquioxide (an organic germanium) has been shown to have a more favorable safety profile. However, past toxicity studies on germanium sesquioxide compounds have not clearly stated the purity of the tested compounds. In the studies reported herein, there was no evidence of mutagenicity in a bacterial reverse mutation test or an in vitro mammalian chromosomal aberration test. There was no genotoxic activity observed in an in vivo mammalian micronucleus test at concentrations up to the limit dose of 2000&#x2009;mg/kg bw/day. In a 90-day repeated-dose oral toxicity study in Han:WIST rats conducted at doses of 0, 500, 1000, and 2000&#x2009;mg/kg bw/day by gavage, there were no mortalities, treatment-related adverse effects, or target organs identified. The no-observed-adverse-effect-level (NOAEL) was determined to be 2000&#x2009;mg/kg bw/day.

Robin A. Reddeman

R&#xf3;bert Gl&#xe1;vits

John R. Endres

Timothy S. Murbach

G&#xe1;bor Hirka

Ad&#xe9;l V&#xe9;rtesi

Erzs&#xe9;bet B&#xe9;res

Ilona Pasics Szakonyin&#xe9;

A Toxicological Evaluation of Germanium Sesquioxide (Organic Germanium)

Agro pesticides are increasingly used worldwide to increase crop production. However, health hazards resulting from human exposure to these chemicals, especially from agricultural areas of developing countries have been a growing concern. The objective of this study was to evaluate the impact of occupational exposure to agro pesticides on the health of farmers in the Buea subdivision, which is one of the major agrarian areas in Cameroon. The study was transversal and involved 90 participants including 58 farmers using pesticides and a reference population of 32 men not involved in occupational use of agro pesticides. The participants were interviewed on agro pesticide use and their health status. Thereafter, blood samples were collected from the participants and used for the assessment of biochemical markers of the liver (alanine aminotransferase and aspartate aminotransferase) and the kidney (creatinine and uric acid) function. Results revealed that farmers frequently used insecticides, fungicides, and herbicides in their farming activities. Farmers reported several acute health symptoms related to pesticides use with the common ones being skin rash, eye irritation, and face burn. When compared to the reference population, the farmers showed significantly elevated (<svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-3.42938pt" id="M1" height="11.7782pt" version="1.1" viewBox="-0.0498162 -8.34882 44.5261 11.7782" width="44.5261pt"><g transform="matrix(.013,0,0,-0.013,0,0)"><path id="g113-113" d="M570 304C570 398 525 448 414 448C385 448 343 445 312 434L329 511L321 518C297 504 262 482 244 460L233 411C195 397 159 381 128 358L135 332C160 347 189 360 224 373L111 -147C97 -210 84 -218 17 -231L13 -257L254 -247L259 -218L233 -216C183 -212 177 -202 189 -142L218 -1C238 -10 266 -12 283 -12C351 3 429 48 483 105C543 168 570 242 570 304ZM482 289C482 161 380 33 304 33C278 33 248 51 233 69L303 396C326 400 352 403 369 403C428 403 482 380 482 289Z"/></g><g transform="matrix(.013,0,0,-0.013,11.342,0)"><path id="g117-91" d="M512 -3V55L134 254V256L512 456V514L75 281V230L512 -3Z"/></g><g transform="matrix(.013,0,0,-0.013,22.605,0)"><path id="g113-49" d="M241 635C89 635 35 457 35 312C35 153 89 -12 240 -12C390 -12 443 166 443 312C443 466 390 635 241 635ZM238 602C329 602 354 454 354 312C354 172 330 22 240 22C152 22 124 173 124 313S148 602 238 602Z"/></g><g transform="matrix(.013,0,0,-0.013,28.845,0)"><path id="g113-47" d="M113 -12C146 -12 170 11 170 46C170 78 146 103 114 103S58 78 58 46C58 11 82 -12 113 -12Z"/></g><g transform="matrix(.013,0,0,-0.013,31.809,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,38.049,0)"><path id="g113-50" d="M384 0V27C293 34 287 42 287 114V635C232 613 172 594 109 583V559L157 557C201 555 205 550 205 499V114C205 42 199 34 109 27V0H384Z"/></g></svg>) alanine aminotransferase activity. However, other parameters investigated were not affected significantly. These results suggested that farmers were exposed to 3 different classes of agro pesticides, which induced eye and skin affections. Pesticides exposure resulted in alterations of the liver function hence the increased serum alanine aminotransferase activity. Therefore, there is a need to sensitize the farmers on toxicity and liver alteration potential of agro pesticides and the importance of appropriate protective equipment that may minimize exposure.

Faustin Pascal Tsagu&#x00E9; Manfo

Sharon Asukia Mboe

Edouard Akono Nantia

Ferdinand Ngoula

Ph&#x00E9;lix Bruno Telefo

Paul Fewou Moundipa

Fidelis Cho-Ngwa

Evaluation of the Effects of Agro Pesticides Use on Liver and Kidney Function in Farmers from Buea, Cameroon

Cymbopogon giganteus Chiov. (Poaceae) is a medicinal plant used to treat various diseases in traditional medicine in several African countries. The present study aims to evaluate the oral and inhalation toxicity as well as the mutagenic effects of the essential oil of Cymbopogon giganteus leaves (EOCG) from a sample collected in Benin. Mutagenic potential was assessed by the Ames test using Salmonella typhimurium strains TA98 and TA100. Oral acute toxicity was carried out by administration of a single dose of 2000&#x2009;mg/kg b.w. to Wistar rats while oral subacute toxicity was assessed by daily administration of 50 and 500&#x2009;mg/kg of EOCG for 28 days. Finally, inhalation toxicity was assessed by administration of a single dose of 0.125&#x0025;, 0.5&#x0025;, 2&#x0025; or 5&#x0025; v/v of EOCG emulsions in 0.05&#x0025; v/v lecithin solution in sterile water for the first experiment, and in a second one by administration of single dose of 0.125&#x0025; or 0.5&#x0025; v/v. A broncho-alveolar lavage was performed after 3&#x2009;h or 24&#x2009;h, respectively. The results show that EOCG is not mutagenic on Salmonella typhimurium strains at the highest concentration tested (200&#x2009;&#x03BC;g/plate). In the acute oral toxicity study, EOCG induce neither mortality nor toxicity, showing that the LD50 is greater than 2000&#x2009;mg/kg. The subacute oral toxicity study at both doses did not show any significant difference in body weight, relative organ weight, hematological and/or biochemical parameters or histopathology as compared to the control group. EOCG induced mortality and inflammation in lungs 3&#x2009;h after administration of a single dose of 5&#x0025; or 2&#x0025; v/v. Single doses of 0.125&#x0025; or 0.5&#x0025; v/v did not induce inflammation, cell recruitment nor cytotoxicity in lungs 3&#x2009;h or 24&#x2009;h after administration, suggesting safety at these concentrations. This first report on the in vivo toxicity will be useful to guide safe uses of EOCG.

Habib Toukourou

Francine Uwambayinema

Yousof Yakoub

Birgit Mertens

Anatole Laleye

Dominique Lison

Joelle Quetin-Leclercq

Fernand Gbaguidi

In Vitro and In Vivo Toxicity Studies on Cymbopogon giganteus Chiov. Leaves Essential Oil from Benin

Iron is an essential element and the most abundant trace metal in the body involved in oxygen transport and oxygen sensing, electron transfer, energy metabolism, and DNA synthesis. Excess labile and unchelated iron can catalyze the formation of tissue-damaging radicals and induce oxidative stress. English abstracts were identified in PubMed and Google Scholar using multiple and various search terms based on defined inclusion and exclusion criteria. Full-length articles were selected for systematic review, and secondary and tertiary references were developed. Although bloodletting or phlebotomy remains the gold standard in the management of iron overload, this systematic review is an updated account of the pitfalls of phlebotomy and classical synthetic chelators with scientific justification for the use of natural iron chelators of dietary origin in resource-poor nations.

Orish Ebere Orisakwe

Cecilia Nwadiuto Amadi

Chiara Frazzoli

Management of Iron Overload in Resource Poor Nations: A Systematic Review of Phlebotomy and Natural Chelators

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Journal of Toxicology publishes papers in all areas of toxicological sciences, including the structure, function, and mechanism of agents toxic to humans and/or animals, as well as toxicological medicine, safety evaluation, and environmental health.

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Chief Editor, Professor You-Cheng Hseu, is based at China Medical University. His research focuses on the biology of free radicals, bioactivity in traditional Chinese medicines, and antioxidants and cosmeceutics.

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Journal of Toxicology publishes papers in all areas of toxicological sciences, including the structure, function, and mechanism of agents toxic to humans and/or animals, as well as toxicological medicine, safety evaluation, and environmental health.

Journal of Toxicology