Tetrachloro-1,4-benzoquinone (TCBQ), an active metabolite of pentachlorophenol (PCP), is genotoxic and potentially carcinogenic. As an electrophilic and oxidative molecule, TCBQ can conjugate with deoxyguanosine in DNA molecules and/or impose oxidative stress in cells. In the current study, we investigated the effects of TCBQ on intracellular ROS production, apoptosis, and cytotoxicity against three different subtypes of human breast cancer cells. Luminal A subtype MCF7 (ER<sup>+</sup>, PR<sup>+</sup>, HER2<sup>−</sup>) cells maintained the highest intracellular ROS level and were subjected to TCBQ-induced ROS reduction, apoptosis, and cytotoxicity. HER2 subtype Sk-Br-3 (ER<sup>−</sup>, PR<sup>−</sup>, HER2<sup>+</sup>) cells possessed the lowest intracellular ROS level. TCBQ promoted ROS production, inhibited apoptosis, and elevated cytotoxicity (due to necrosis) against Sk-Br-3 cells. Triple-negative/basal-like subtype MDA-MB-231 cells were less sensitive towards TCBQ treatment. Therefore, the effect of prolonged exposure to PCP and its active metabolites on cancer growth is highly cancer-cell-type specific.

Binbing Ling

Bosong Gao

Jian Yang

Evaluating the Effects of Tetrachloro-1,4-benzoquinone, an Active Metabolite of Pentachlorophenol, on the Growth of Human Breast Cancer Cells

<i>Background</i>. Cement dust inhalation is associated with deleterious health effects. The impact of cement dust exposure on the peak expiratory flow rate (PEFR), liver function, and some serum elements in workers and residents near cement factory were assessed.<i> Methods</i>. Two hundred and ten subjects (50 workers, 60 residents, and 100 controls) aged 18–60 years were studied. PEFR, liver function <svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-2.26807pt" id="M1" height="11.5564pt" version="1.1" viewBox="-0.0498162 -9.28833 4.62754 11.5564" width="4.62754pt"><g transform="matrix(.013,0,0,-0.013,0,0)"><path id="g113-124" d="M293 -169V-141C218 -131 209 -90 209 -44C209 19 222 85 222 152C222 207 198 255 139 269V273C199 286 222 334 222 388C222 454 209 523 209 588C209 632 218 671 293 681V709C234 709 148 695 148 577C147 513 155 438 155 372C155 337 152 291 64 285V256C152 250 155 204 155 169C156 105 148 31 148 -41C148 -157 234 -169 293 -169Z"/></g></svg>aspartate and alanine transaminases (AST and ALT) and total and conjugated bilirubin (TB and CB)<svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-2.26807pt" id="M2" height="11.5564pt" version="1.1" viewBox="-0.0498162 -9.28833 4.62754 11.5564" width="4.62754pt"><g transform="matrix(.013,0,0,-0.013,0,0)"><path id="g113-126" d="M283 255V284C195 290 192 337 192 375C192 436 200 508 200 580C200 696 116 709 54 709V681C127 671 139 634 139 588C138 524 125 452 125 387C125 333 149 286 209 272V268C148 253 125 206 125 151C126 87 139 16 139 -47C139 -92 127 -131 54 -141V-169C115 -169 200 -152 200 -41C200 32 192 104 192 164C192 202 195 249 283 255Z"/></g></svg>, and serum elements <svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-2.26807pt" id="M3" height="11.5564pt" version="1.1" viewBox="-0.0498162 -9.28833 4.62754 11.5564" width="4.62754pt"><g transform="matrix(.013,0,0,-0.013,0,0)"><use xlink:href="#g113-124"/></g></svg>lead (Pb), copper (Cu), manganese (Mn), iron (Fe), cadmium (Cd), selenium (Se), chromium (Cr), zinc (Zn), and arsenic (As)<svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-2.26807pt" id="M4" height="11.5564pt" version="1.1" viewBox="-0.0498162 -9.28833 4.62754 11.5564" width="4.62754pt"><g transform="matrix(.013,0,0,-0.013,0,0)"><use xlink:href="#g113-126"/></g></svg> were determined using peak flow meter, colorimetry, and atomic absorption spectrometry, respectively. Data were analysed using ANOVA and correlation at <svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-3.42938pt" id="M5" 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="g117-34" d="M535 323V373H52V323H535ZM535 138V188H52V138H535Z"/></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="g113-54" d="M153 550H386L412 615L406 623H120L82 318C104 327 142 338 184 338C294 338 347 275 347 187C347 112 305 39 221 39C160 39 119 71 97 89C88 97 80 96 71 90C59 80 50 67 49 57C48 45 52 36 66 23C80 9 123 -12 169 -12C221 -11 288 15 342 59C403 109 431 165 431 225C431 308 366 395 238 395C212 395 165 379 127 364L153 550Z"/></g></svg>.<i> Results</i>. The ALT, TB, CB, Pb, As, Cd, Cr, Se, Mn, and Cu were significantly higher and PEFR, Fe, and Zn lower in workers and residents compared to controls (<svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-3.42938pt" id="M6" 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)"><use xlink:href="#g113-113"/></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)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,28.845,0)"><use xlink:href="#g113-47"/></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)"><use xlink:href="#g113-54"/></g></svg>). Higher levels of ALT, AST, and Fe and lower levels of Pb, Cd, Cr, Se, Mn, and Cu were seen in cement workers compared to residents (<svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-3.42938pt" id="M7" 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)"><use xlink:href="#g113-113"/></g><g transform="matrix(.013,0,0,-0.013,11.342,0)"><use xlink:href="#g117-91"/></g><g transform="matrix(.013,0,0,-0.013,22.605,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,28.845,0)"><use xlink:href="#g113-47"/></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)"><use xlink:href="#g113-54"/></g></svg>). Negative correlation was observed between duration of exposure and PEFR (<svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-0.3499298pt" id="M8" height="8.69875pt" version="1.1" viewBox="-0.0498162 -8.34882 56.2178 8.69875" width="56.2178pt"><g transform="matrix(.013,0,0,-0.013,0,0)"><path id="g113-115" d="M393 379C402 394 400 411 393 422C384 437 365 448 348 448C301 448 237 372 186 285H182L193 335C210 408 205 448 178 448C150 448 80 402 29 344L45 321C80 355 114 373 122 373C128 373 130 365 124 330C106 228 76 98 50 -5L57 -12C82 -5 112 3 132 6L172 203C196 256 234 304 254 329C275 355 293 367 306 367C318 367 330 360 342 348C347 343 355 343 365 350S386 367 393 379Z"/></g><g transform="matrix(.013,0,0,-0.013,9.12,0)"><use xlink:href="#g117-34"/></g><g transform="matrix(.013,0,0,-0.013,20.383,0)"><path id="g117-33" d="M535 230V280H52V230H535Z"/></g><g transform="matrix(.013,0,0,-0.013,28.042,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,34.282,0)"><use xlink:href="#g113-47"/></g><g transform="matrix(.013,0,0,-0.013,37.246,0)"><path id="g113-53" d="M456 178V225H360V632H320C217 496 115 347 20 206V178H280V106C280 40 276 34 189 27V0H445V27C364 34 360 39 360 106V178H456ZM280 225H82C149 335 214 431 278 520H280V225Z"/></g><g transform="matrix(.013,0,0,-0.013,43.487,0)"><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><g transform="matrix(.013,0,0,-0.013,49.727,0)"><path id="g113-55" d="M137 343C167 482 260 545 321 574C357 591 397 603 429 609L423 641C382 634 335 622 295 608C189 570 37 457 37 238C37 84 125 -12 242 -12C362 -12 447 89 447 209C447 311 374 393 267 393C247 393 226 386 204 376L137 343ZM227 337C318 337 361 256 361 173C361 105 336 22 258 22C176 22 126 120 126 240C126 266 127 291 132 310C155 323 189 337 227 337Z"/></g></svg>, <svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-3.42938pt" id="M9" height="11.7782pt" version="1.1" viewBox="-0.0498162 -8.34882 50.7895 11.7782" width="50.7895pt"><g transform="matrix(.013,0,0,-0.013,0,0)"><use xlink:href="#g113-113"/></g><g transform="matrix(.013,0,0,-0.013,11.342,0)"><use xlink:href="#g117-34"/></g><g transform="matrix(.013,0,0,-0.013,22.605,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,28.845,0)"><use xlink:href="#g113-47"/></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)"><use xlink:href="#g113-50"/></g><g transform="matrix(.013,0,0,-0.013,44.289,0)"><use xlink:href="#g113-55"/></g></svg>) in cement workers.<i> Conclusions</i>. Cement dust inhalation may be associated with alterations in serum elements levels and lung and liver functions while long term exposure lowers peak expiratory flow rate. 

Egbe Edmund Richard

Nsonwu-Anyanwu Augusta Chinyere

Offor Sunday Jeremaiah

Usoro Chinyere Adanna Opara

Etukudo Maise Henrieta

Egbe Deborah Ifunanya

Cement Dust Exposure and Perturbations in Some Elements and Lung and Liver Functions of Cement Factory Workers

A study was designed to investigate ameliorates effect of combined vitamins C and E able to against depot-medroxyprogesterone acetate- (DMPA-) induced ovarian oxidative stress in rat. Twenty-five female Wistar rats were divided into the following groups (<svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-0.2063999pt" id="M1" height="8.32035pt" version="1.1" viewBox="-0.0498162 -8.11395 27.8368 8.32035" width="27.8368pt"><g transform="matrix(.013,0,0,-0.013,0,0)"><path id="g113-111" d="M495 86L479 114C446 82 419 66 409 66C401 66 401 72 406 97C420 166 436 231 453 297C489 435 454 448 428 448C406 448 384 439 354 422C305 394 222 327 161 247H159L183 345C200 415 194 448 173 448C143 448 82 410 23 351L38 325C64 349 95 371 105 371C111 371 116 365 109 336L25 -4L31 -12C50 -4 77 3 107 9C119 69 132 122 145 168C197 254 321 381 370 381C387 381 393 374 378 305L329 95C309 17 320 -12 345 -12C372 -12 430 19 495 86Z"/></g><g transform="matrix(.013,0,0,-0.013,10.158,0)"><path id="g117-34" d="M535 323V373H52V323H535ZM535 138V188H52V138H535Z"/></g><g transform="matrix(.013,0,0,-0.013,21.421,0)"><path id="g113-54" d="M153 550H386L412 615L406 623H120L82 318C104 327 142 338 184 338C294 338 347 275 347 187C347 112 305 39 221 39C160 39 119 71 97 89C88 97 80 96 71 90C59 80 50 67 49 57C48 45 52 36 66 23C80 9 123 -12 169 -12C221 -11 288 15 342 59C403 109 431 165 431 225C431 308 366 395 238 395C212 395 165 379 127 364L153 550Z"/></g></svg> rats each): control (untreated) (C); depot-medroxyprogesterone acetate (DMPA); DMPA plus green vitamin C (at dose of 0.2 mg/gram; 0.4 mg/gram; 0.8 mg/gram) and vitamin E (0.04 IU/gram). The treatment with combined vitamins C and E was performed for four weeks. Analysis of malondialdehyde (MDA) level as a marker of oxidative stress was done colorimetrically. Analysis of SOD level was done by enzyme linked immunosorbent assay (ELISA) technically. This increase in ovarium MDA was significantly (<svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-0.6370001pt" id="M2" height="9.2729pt" version="1.1" viewBox="-0.0498162 -8.6359 44.8393 9.2729" width="44.8393pt"><g transform="matrix(.013,0,0,-0.013,0,0)"><path id="g113-81" d="M600 480C600 590 528 650 384 650H143L137 622C222 614 225 607 210 531L130 127C113 41 106 36 23 28L17 0H294L300 28C204 36 195 42 212 127L243 284L314 263C327 263 339 263 352 264C465 271 600 337 600 480ZM508 481C508 351 402 304 329 304C289 304 265 311 250 317L295 559C302 594 310 606 323 611C335 616 350 619 367 619C455 619 508 573 508 481Z"/></g><g transform="matrix(.013,0,0,-0.013,11.658,0)"><path id="g117-91" d="M512 -3V55L134 254V256L512 456V514L75 281V230L512 -3Z"/></g><g transform="matrix(.013,0,0,-0.013,22.921,0)"><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,-0.013,29.161,0)"><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,-0.013,32.125,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,38.365,0)"><use xlink:href="#g113-54"/></g></svg>) attenuated by medium dose treatments of combined vitamins C and E. DMPA insignificantly decreased SOD levels compared to the untreated group. This decrease in ovarian SOD level was significantly attenuated by all doses of the combined vitamins C and E. In conclusion, DMPA induces ovarian oxidative stress. Combined vitamins C and E prohibit the increase in ovarian lipid peroxidation, at least in part by modulating of superoxide dismutase. Therefore, this may provide an antioxidant therapy for attenuating the ovarian toxicity found in the DMPA therapy.

Atik Ismiyati

I. Wayan Arsana Wiyasa

Dwi Yuni Nur Hidayati

Protective Effect of Vitamins C and E on Depot-Medroxyprogesterone Acetate-Induced Ovarian Oxidative Stress In Vivo

Cyclosporine is considered one of the common worldwide immunosuppressive drugs that are used for allograft rejection prevention. However, articles that address adverse effects of cyclosporine use on the vital organs such as lung are still few. This study aims to investigate pulmonary toxic effect of cyclosporine in rats by assessment of pulmonary histopathological changes using light and electron microscope examination. Sixty male adult albino rats were divided into three groups; each group consists of twenty rats. The first received physiological saline while the second and third groups received 25 and 40&#x2009;mg/kg/day of cyclosporine, respectively, by gastric gavage for forty-five days. Cyclosporine reduced the lung and body weight with shrinkage or pyknotic nucleus of pneumocyte type II, degeneration of alveoli and interalveolar septum beside microvilli on the alveolar surface, emphysema, inflammatory cellular infiltration, pulmonary blood vessels congestion, and increase of fibrous tissues in the interstitial tissues and around alveoli with negative Periodic Acid-Schiff staining. Prolonged use of cyclosporine induced pulmonary ultrastructural and histopathological changes with the lung and body weight reduction depending on its dose.

Said Said Elshama

Ayman El-Meghawry EL-Kenawy

Hosam-Eldin Hussein Osman

Histopathological Study of Cyclosporine Pulmonary Toxicity in Rats

Microcystins are toxic molecules produced by cyanobacterial blooms due to water eutrophication. Exposure to microcystins is a global health problem because of its association with various other pathological effects and people all over the world are exposed to microcystins on a regular basis. Evidence shows that microcystin-LR (MC-LR) may adversely affect the immune system, but its specific effects on immune functions are lacking. In the present review, immunotoxicological effects associated with MC-LR in animals, humans, and<i> in vitro</i> models have been reported. Overall, the data shows that chronic exposure to MC-LR has the potential to impair vital immune responses which could lead to increased risk of various diseases including cancers. Studies in animal and<i> in vitro</i> models have provided some pivotal understanding into the potential mechanisms of MC-LR related immunotoxicity suggesting that further investigation, particularly in humans, is required to better understand the relationship between development of disease and the MC-LR exposure.

Yaqoob Lone

Mangla Bhide

Raj Kumar Koiri

Microcystin-LR Induced Immunotoxicity in Mammals

Nephrotoxicity is one of the limiting factors for using doxorubicin (DOX). Interleukin 1 has major role in DOX-induced nephrotoxicity, so we investigated the effect of interleukin 1 receptor antagonist diacerein (DIA) on DOX-induced nephrotoxicity. DIA (25 and 50&#x2009;mg/kg/day) was administered orally to rats for 15 days, in the presence or absence of nephrotoxicity induced by a single intraperitoneal injection of DOX (15&#x2009;mg/kg) at the 11th day. We measured levels of serum urea, creatinine, renal reduced glutathione (GSH), malondialdehyde (MDA), total nitrites (NO<sub><i>x</i></sub>), catalase, and superoxide dismutase (SOD). In addition, caspase-3, tumor necrosis factor alpha (TNF<i>&#x3b1;</i>), nuclear factor kappa B (NF<i>&#x3ba;</i>B) expressions, and renal histopathology were assessed. Our results showed that DOX-induced nephrotoxicity was ameliorated or reduced by both doses of DIA, but diacerein high dose (DHD) showed more improvement than diacerein low dose (DLD). This protective effect was manifested by significant improvement in all measured parameters compared to DOX treated group by using DHD. DLD showed significant improvement of creatinine, MDA, NO<sub><i>x</i></sub>, GSH, histopathology, and immunohistochemical parameters compared to DOX treated group.

Marwa M. M. Refaie

Entesar F. Amin

Nashwa F. El-Tahawy

Aly M. Abdelrahman

Possible Protective Effect of Diacerein on Doxorubicin-Induced Nephrotoxicity in Rats

Current lifestyle, stress, and pollution have dramatically enhanced the progression of several diseases in human. Globally, scientists are looking for therapeutic agents that can either cure or delay the onset of diseases. Medicinal plants from time immemorial have been used frequently in therapeutics. Of many such plants, fenugreek is one of the oldest herbs which have been identified as an important medicinal plant by the researchers around the world. It is potentially beneficial in a number of diseases such as diabetes, hypercholesterolemia, and inflammation and probably in several kinds of cancers. It has industrial applications such as synthesis of steroidal hormones. Its medicinal properties and their role in clinical domain can be attributed to its chemical constituents. The 3 major chemical constituents which have been identified as responsible for principle health effects are galactomannan, 4-OH isoleucine, and steroidal saponin. Numerous experiments have been carried out<i> in vivo</i> and<i> in vitro</i> for beneficial effects of both the crude chemical and of its active constituent. Due to its role in health care, the functional food industry has referred to it as a potential nutraceutical. This paper is about various medicinal benefits of fenugreek and its potential application as therapeutic agent against several diseases.

Shivangi Goyal

Nidhi Gupta

Sreemoyee Chatterjee

Investigating Therapeutic Potential of <i>Trigonella foenum-graecum</i> L. as Our Defense Mechanism against Several Human Diseases

Cancer is an inevitable matter of concern in the medicinal chemistry era. Chalcone is the well exploited scaffold in the anticancer domain. The molecular mechanism of chalcone at cellular level was explored in past decades. This mini review provides the most recent updates on anticancer potential of chalcones.

Manik Das

Kuntal Manna

Chalcone Scaffold in Anticancer Armamentarium: A Molecular Insight

About this journal

<p><em>Journal of Toxicology</em> 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.</p>


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<p>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.</p>


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Journal of Toxicology - Table of contents 2016

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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