Mitochondrial Dysfunction Associated with Doxorubicin

Cancer prevalence is scaling up each year. Anthracycline groups are still the best chemotherapeutic agent. The most popular anticancer drug in the group is doxorubicin (DOX). Unfortunately, DOX has potent toxicity on noncancerous tissues, e.g., heart, kidneys, etc. However, it is well documented that the severest toxicity of the drug affects heart tissue. Of course, some reasons have been suggested why and/or how the heart is so vulnerable to toxicity. The primary mechanism responsible for DOX’s cardiospecific toxicity remains unidentified so far; however, mitochondrial dysfunction induced by DOX is now considered one of the leading reasons for DOX’s toxicities and undesired side effects. Mitochondrial reactive oxygen production in the heart is a significant contributor to developing mitochondrial dysfunction-exposed DOX based on a variety of evidence. The objective of this review chapter is to critically evaluate and highlight the role of mitochondria in the development of DOX-induced cardiotoxicity

Pyrethroid Insecticides as the Mitochondrial Dysfunction Inducers

Pyrethroids are used to decrease vector-based health concerns and to increase field yield against agricultural pests. Their metabolism is a concern to disrupt a cell’s homeostatic machinery via reactive oxygen species (ROS) production. They interact with lipid membranes to damage the fine balance between membrane lipids and membrane proteins, especially mitochondrial substrate transporters and electron carriers. Pyrethroids cause a shift in the metabolic energy production strategy, resulting in ROS production and intracellular lipid deposition. The change of open/closed conformation of some mitochondrial membrane proteins increases the vulnerability of mitochondria to Ca2+ ions. Membrane lipid fluidity change is also a concern because of permeability to the substrates and ions to produce energy and other substrates necessary for the cell. Pyrethroids can change the Ca2+ signaling and its interaction with ROS signals via disruption of the fine balance between endoplasmic reticulum and mitochondria. They can disrupt the mitochondrial DNA (mtDNA) via their hydrophobic nature or their ROS production capacity. In conclusion, mitochondria are the center of pyrethroid toxicity, and dysfunction of this organelle via pyrethroid toxicity plays an important role in the fate of cell. Their lipophilic and pro-oxidative nature together with Ca2+ homeostasis plays a synergistic role in this mitochondrial effect

Oksidacijski i apoptotski učinci fluoksetina i njegova metabolita norfluoksetina u vodenbuhe Daphnia magna

The aim of this study was to investigate the oxidative and apoptotic potential of fluoxetine, a widely used antidepressant in Turkey and the world, and of its metabolite norfluoxetine on a model non-target organism, Daphnia magna to see how exposure to this group of antidepressants (specific serotonin reuptake inhibitors) could affect the aquatic environment in which they end up. Juvenile D. magna specimens were chronically exposed to fluoxetine and norfluoxetine alone and in combination at concentrations found in the aquatic environment (0.091 and 0.011 μg/L, respectively) and to their 10-fold environmental concentrations for 21 days. Another group of 17-day-old animals were subacutely exposed to 100-fold environmental concentrations for four days. After exposure, we measured their glutathione peroxidase (GPx) and cholinesterase (ChE) activities, thiobarbituric acid-reactive substances (TBARS), and total protein content spectrophotometrically, while mitochondrial membrane potential (MMP) was analysed by fluorescence staining, and cytochrome c and ERK1/2 protein content by Western blotting. This is the first-time cytochrome c and ERK1/2 were determined at the protein level in D. magna. We also measured their carapace length, width, and caudal spine length microscopically. At environmental concentrations fluoxetine and norfluoxetine caused an increase in ChE activity and brood production. They also caused a decrease in juvenile carapace length, width, and caudal spine length and depolarized the mitochondrial membrane. At 10-fold environmental concentrations, GPx activity, lipid peroxidation levels, cytochrome c, and ERK1/2 protein levels rose. The most pronounced effect was observed in D. magna exposed to norfluoxetine. Norfluoxetine also decreased brood production. Similar effects were observed with subacute exposure to 100-fold environmental concentrations. However, total protein content decreased. All this confirms that fluoxetine and norfluoxetine have oxidative and apoptotic potential in D. magna. Daphnia spp. have a great potential to give us precious insight into the mechanisms of environmental toxicants, but there is still a long way to go before they are clarified in these organisms.Cilj je ovoga istraživanja bio utvrditi oksidacijski i apoptotski potencijal fluoksetina, antidepresiva raširenoga u Turskoj i svijetu, i njegova metabolita norfluoksetina na modelu vodenbuhe Daphnia magna koji nije ciljani organizam djelovanja spojeva. Također smo željeli vidjeti kako izloženost toj skupini antidepresiva (specifičnih inhibitora ponovne pohrane serotonina) može utjecati na vodeni okoliš u kojem oni završe. Mlade jedinke vodenbuhe bile su izložene fluoksetinu (0,091 μg/L) i norfluoksetinu (0,011 μg/L), odvojeno i u kombinaciji, pri koncentracijama zamijećenima u okolišu I deseterostrukim okolišnim koncentracijama u trajanju od 21 dan (kronična izloženost). Jedna je skupina 17 dana starih vodenbuha također bila izložena stostrukoj okolišnoj koncentraciji u trajanju od četiri dana (subakutna izloženost). Potom su u životinja spektrofotometrijom izmjerene aktivnosti enzima glutation peroksidaze (GPx) i kolinesteraza (ChE) te razine reaktivnih tvari tiobarbituratne kiseline (TBARS) i ukupnih proteina. Potencijal mitohondrijske membrane (MMP) utvrđen je fluorescencijom, a proteini citokrom c i ERK1/2 Western blot metodom. Ovo je prvi put da su se u vodenbuhi citokrom c i ERK1/2 utvrđivali na razini proteina. Također je mikroskopski izmjerena dužina i širina oklopa i dužina repne bodlje vodenbuha. Pri okolišnim koncentracijama fluoksetin i norfluoksetin doveli su do povišene aktivnost ChE i većeg razmnožavanja te smanjenja (dužine i širine) karapaksa i repne bodlje u podmlatka i depolarizacije mitohondrijske membrane. Pri deseterostrukim okolišnim koncentracijama porasle su razine aktivnosti GPx, lipidne peroksidacije, citokroma c i ERK1/2 proteina. Norfluoksetin je pritom iskazao najsnažnije djelovanje te doveo do pada razmnožavanja. Slični su učinci primijećeni kod subakutne izloženosti stostrukim okolišnim koncentracijama fluoksetina i norfluoksetina, osim što je ona dovela i do pada ukupnih proteina. Naši rezultati potvrđuju da fluoksetin i norfluoksetin imaju oksidacijski i apoptotski učinak u vodenbuhe. Taj životinjski model može odlično poslužiti za stjecanje uvida u mehanizme toksičnoga djelovanja tvari u okolišu, no potrebna su daljnja istraživanja prije nego što ti mehanizmi postanu potpuno jasni

Usporedba kemijskih i bioloških značajki propolisa pčelinje pasmine Apis mellifera caucasica iz turskih provincija Ardahana i Erzuruma

The aim of this study was to compare the biological activities of ethanolic propolis extracts of Apis mellifera caucasica obtained from Ardahan and Erzurum provinces of Turkey. Samples were tested for antioxidant, anticytotoxic, anticarcinogenic, antibacterial, and antifungal potentials using different techniques. Propolis samples from the two provinces had different mineral and organic compositions related to their geographical origin. The ferric reducing antioxidant power (FRAP) test showed superiority of Ardahan propolis over the Erzurum. Regardless of origin and the presence of mitomycin C in the culture medium, propolis enhanced human peripheral lymphocyte viability, which depended on the duration and propolis concentration. Antiperoxidative activity on MCF-7 breast cancer cells was concentrationdependent. Erzurum propolis showed the highest anticarcinogenic activity at the concentrations of 62.5 μg/mL and 125 μg/ mL, which dropped at higher concentrations. All propolis samples also showed antibacterial activity against the tested human pathogens similar to ampicillin and penicillin controls, except for Pseudomonas aeruginosa. However, they did not exert any antifungal activity against Candida albicans and Yarrowia lipolytica. In conclusion, propolis samples from both provinces showed promising biological activities, but further research should focus on finding the right concentrations for optimal effect and include the cell necrosis pathway to get a better idea of the anticarcinogenic effects.Cilj je ovoga istraživanja bio usporediti biološku aktivnost etanolnih ekstrakata propolisa pčelinje pasmine Apis mellifera caucasica iz dviju turskih provincija: Ardahana i Erzuruma. Testirana su njihova antioksidacijska, anticitotoksična, antikancerogena, antibakterijska i antifungalna svojstva. Uzorci iz tih dviju provincija razlikovali su se u mineralnom i organskom sastavu koji je odražavao njihovo zemljopisno podrijetlo. Test redukcije željeza/antioksidacijske snage (engl. ferric reducing antioxidant power, krat. FRAP) otkrio je superiornost ardahanskoga propolisa nad erzurumskim, no bez obzira na podrijetlo i prisutnost mitomicina C u mediju, oba su propolisa povećala vijabilnost ljudskih perifernih limfocita, a učinak je ovisio o koncentraciji i trajanju. Propolis iz Erzuruma iskazao je najveću antikancerogenu aktivnost u koncentracijama od 62,5 i 125 μg/mL, no ona se smanjila s višim koncentracijama. Oba su propolisa također iskazala antibakterijsku aktivnost sličnu ampicilinskoj i penicilinskoj kontroli, osim kad se radilo o bakteriji Pseudomonas aeruginosa. Međutim, oba su zakazala protiv plijesni Candida albicans i Yarrowia lipolytica. Može se zaključiti da uzorci propolisa iz obiju provincija pružaju obećavajuće biološke aktivnosti, no u daljnja istraživanja, koja se trebaju usmjeriti na traženje optimalnih koncentracija za postizanje željenog učinka, treba uključiti i nekrotični put u mehanizmu djelovanja kako bi se stekao bolji uvid u njihovo antikancerogeno djelovanje

Antioksidativni učinci N-acetilcisteina, lipoične kiseline, taurina i kurkumina u mišićnom tkivu šarana (Cyprinus carpio L.) tretiranih kadmijem

We investigated the muscle tissue of a teleost Cyprinus carpio L. to find out whether N-acetylcysteine (NAC), alpha-lipoic acid (LA), taurine (TAU), and curcumin (CUR) were able to counteract oxidative stress induced by acute exposure to cadmium (Cd). The muscle tissue was dissected 96 h after a single intraperitoneal injection of Cd (5 mg kg-1) and of antioxidant substances (50 mg kg-1). Using spectrophotometry, we determined the glutathione redox status, lipid peroxidation levels and the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione disulphide reductase (GR). Accumulation of Cd in the muscle was analysed using inductively coupled plasma - optical emission spectrometry (ICP-OES). All substances lowered Cd levels in the following order of effi ciency; LA=NAC>TAU=CUR. Cadmium increased SOD activity, but CAT activity declined, regardless of antioxidant treatment. Treatment with CUR induced GPx activity. Treatment with TAU lowered Cd due to higher total glutathione (tGSH). The most effective substances on lipid peroxidation were LA and NAC due to a greater Cd-lowering potential. It seems that the protective role of TAU, LA, and NAC is not necessarily associated with antioxidant enzymes, but rather with their own activity.Cilj istraživanja bio je utvrditi mogu li N-acetilcistein (NAC), α-lipoična kiselina (LA), taurin (TAU) i kurkumin (CUR) svojim antioksidativnim djelovanjem smanjiti razinu oksidativnog stresa u mišićnom tkivu šarana (Cyprinus carpio L.) akutno otrovanih kadmijem. Uzorci mišićnog tkiva skupljeni su 96 h nakon što su ribama intraperitonealno injicirani kadmij (5 mg kg-1) i ispitivani antioksidansi (50 mg kg-1). Primjenom spektrofotometrijskih metoda izmjereni su redoks status glutationa, razine lipidne peroksidacije te aktivnosti enzima superoksid dismutaze (SOD), katalaze (CAT), glutation peroksidaze (GPx) i glutation disulfi d reduktaze (GR). Maseni udio kadmija u mišićnom tkivu izmjeren je s pomoću metode induktivno spregnute plazme – optičke emisijske spektrometrije (ICP-OES). Ispitivani spojevi smanjili su nakupljanje kadmija u tkivu šarana sljedećim redoslijedom: LA=NAC>TAU=CUR. Tretman šarana kadmijem izazvao je porast aktivnosti SOD, ali se aktivnost CAT smanjila bez obzira na primjenu antioksidativnih spojeva. Dodatak CUR pojačao je aktivnost GPx. Dodatak TAU povećao je razinu ukupnoga glutationa te smanjio nakupljanje kadmija. Svi spojevi osim CUR smanjili su razinu lipidne peroksidacije te pretpostavljamo da su LA i NAC pridonijeli detoksifi kaciji kadmija. Rezultati istraživanja upućuju na to da testirani spojevi, osim CUR, imaju antioksidativni učina

Etoxazolenin Oreochromis niloticus'da karaciğerde GPT, AChE, ATPaz, antioksidant enzim aktiviteleri ve lipid peroksşdasyonuna etkileri

TEZ3980Tez (Yüksek Lisans) -- Çukurova Üniversitesi, Adana, 20026.Kaynakça (s. 56-63) var.v, 63 s. ; 30 cm.

Oreochromis niloticus'da karaciğer ve böbrek dokularında fenthionun nac ve bso modülatörlüğünde glutatyon metabolizmasına oksidatif etkileri

TEZ6390Tez (Doktora) -- Çukurova Üniversitesi, Adana, 2007.Kaynakça (s.83-94) var.xii, 95 s. : res. ; 29 cm.This study was designated to understand the effects of organophosphate insecticide and avicide fenthion on cellular redox state and the role of GSH on this process in the liver and kidney of Oreochromis niloticus. NAC and BSO, modulators of GSH metabolism, were intraperitoneally injected and tGSH, GSH, GSSG and MDA levels, GSH/GSSG ratio and GPx, GR, GST and ?-GT enzyme activities were measured spectrophotometrically at 24-, 48- and 96-h. Depuration periods of 24-, 48- and 96-h were also maintained to evaluate the changes in fenthion toxicity. Fenthion increased GST and decreased GPx activities and caused a time-dependent depletion in tGSH and GSSG levels in the liver tissue during treatment periods. Decline in tGSH, GSH and GSSG levels, and elevation in GST and ?-GT enzyme activities by BSO injection were observed. No change was found by fenthion exposure in lipid peroxidation levels in the liver tissue, while NAC injection caused a significant decrease in these levels. A significant decrease was observed tGSH and GSH levels and GST enzyme activities in the kidney tissue during treatment periods. On the contrary to liver tissue, a significant increase was observed in tGSH and GSH levels and GST activity in kidney by BSO. NAC application eliminated the decreasing effects of fenthion on GST activity in this tissue. Increasing effect of fenthion on lipid peroxidation levels was multiplied by BSO and alleviated by NAC. Decline in tGSH and GSH levels which occurred in treatment period were maintained in both tissues during depuration periods; and elevation in lipid peroxidation levels were observed during same periods. GST and GPx enzyme activities and tGSH and GSH levels were found to be useful indicators to evaluate the effects of fenthion. BSO injection revealed the significance of GST mediated GSH conjugation on the detoxification process of fenthion and its phase I metabolites. NAC application was useful to avoid the toxic effects of fenthion in acute periods, while it caused an increase in the oxidative toxicity of fenthion in prolonged periods. Depuration period for 96-h was not adequate to eliminate the fenthion-induced changes.Bu çalışmada organofosforlu insektisid ve avisid fenthionun Oreochromis niloticus'da karaciğer ve böbrek dokularında hücresel redoks durumuna etkilerinin ve bu süreçte GSH'ın rolünün aydınlatılması amaçlanmıştır. Bu amaçla GSH modülatörleri olan bütiyonin sülfoksimin (BSO) ve Nasetilsisteinin (NAC) intraperitonal uygulamalarında 24, 48 ve 96 saatlik etkilerde tGSH, GSH, GSSG ve MDA miktarları, GSH/GSSG oranı ile GPx, GR, GST ve ?-GT enzim aktiviteleri spektrofotometrik yöntemlerle incelenmiştir. 24, 48 ve 96 saat depurasyon uygulaması ile fenthion toksisitesindeki değişimler de incelenmiştir. Etki sürecinde fenthion karaciğer dokusunda süreye bağımlı olarak tGSH ve GSSG miktarlarının azalmasına neden olurken GST aktivitesinin artmasına ve GPx aktivitesinin azalmasına yol açmıştır. BSO uygulaması tGSH, GSH ve GSSG miktarlarının azalmasına ve GSH/GSSG oranının ve GST ve ?-GT enzim aktivitelerinin artmasına neden olmuştur. Karaciğer dokusunda fenthion etkisiyle lipid peroksidasyonunda değişim saptanmazken, NAC uygulaması lipid peroksidasyonunu azaltmıştır. Böbrek dokusunda etki sürecinde fenthion tGSH ve GSH miktarlarının ve GST aktivitesinin düşmesine neden olmuştur. BSO uygulaması karaciğer dokusunun aksine böbrek dokusunda tGSH ve GSH miktarlarının ve GST aktivitesinin yükselmesine yol açmıştır. NAC uygulaması böbrekte fenthionun GST azaltıcı etkisini baskılamıştır. Fenthion başlangıçta lipid peroksidasyonunun artmasına neden olurken NAC bu etkiyi baskılamış, BSO ise etkinin artmasına neden olmuştur. Depurasyon sürecinde karaciğer ve böbrek dokularında etki sürecinde meydana gelen tGSH ve GSH azalmaları devam etmiş ve lipid peroksidasyonunda artışlar meydana gelmiştir. GST ve GPx enzim aktiviteleri ile tGSH ve GSH miktarları fenthion etkisinde indikatör parametreler olarak belirlenmiştir. BSO uygulaması ile fenthionun ve faz-I metabolitlerinin detoksifikasyonunda karaciğerde GST aracılıklı GSH konjugasyonunun önemli olduğu ilk kez bu çalışmayla ortaya konmuştur. Kısa sürede toksisiteden korunmaya yardımcı olan NAC uzun sürede toksik etkilerin artışına neden olmaktadır. 96 saatlik depurasyon uygulaması fenthionun toksik etkilerinin giderilmesinde yeterli olmamıştır.Bu çalışma Ç.Ü. Bilimsel Araştırma Projeleri Birimi Tarafından Desteklenmiştir. Proje No:FEF2003D1

Tissue-specific effects of fenthion on glutathione metabolism modulated by NAC and BSO in Oreochromis niloticus

WOS: 000282247200003PubMed ID: 20550428Introduction: The present study was designed to understand the effects of organophosphate (OP) insecticide and avicide fenthion on cellular redox status and the role of reduced glutathione (GSH) on fenthion toxicity in the liver and kidney of Oreochromis niloticus as a model organism. N-acetylcysteine (NAC) and buthionine sulfoximine (BSO) were injected intraperitoneally to fenthion-exposed fish as modulators of GSH metabolism. GSH redox status, GSH-related enzyme activities, and thiobarbituric acid reactive substances (TBARS) contents were then measured spectrophotometrically at 24, 48, and 96 hours. To assess recovery from fenthion exposure, similar analyses were performed on fish transferred to non-treated water for 24, 48, and 96 hours. Results: Fenthion increased glutathione S-transferase (GST; EC 2.5.1.18) activity and caused changes in total GSH (tGSH), GSH and oxidized glutathione (GSSG) contents and glutathione peroxidase (GPx; EC 1.11.1.9) specific activity in the liver tissue over time. Increases observed in tGSH and GSSG contents at 24 hours were decreased by fenthion treatment at 96 hours. BSO caused a sharp decline in liver tGSH, GSH, and GSSG contents and an elevation in GST and gamma-glutamyl transpeptidase (gamma-GT; EC 2.3.2.2) enzyme activities. A significant decrease was observed in tGSH and GSH contents and, also, GST enzyme activities in the kidney at 48-hour fenthion treatment. On the contrary to the liver, a significant increase was observed in tGSH and GSH contents in the kidney by BSO injection. NAC application eliminated the decreasing effects of fenthion on GST activity in this tissue. NAC injection caused decreases in lipid peroxidation (LPO) levels. Decline in tGSH and GSH contents were maintained in the liver during the recovery period, and elevations in LPO levels in the kidney were observed during the same period. Conclusions: In conclusion, tissue-specific and time-dependent GSH redox status disturbance of fenthion were observed. BSO revealed the significance of GST-mediated GSH conjugation on the detoxification process of fenthion. NAC seemed useful to avoid the fenthion-related oxidative toxicity.Cukurova University Scientific Research CommissionCukurova University [FEF2003D19]Financial support for this project (FEF2003D19) from the Cukurova University Scientific Research Commission is gratefully acknowledged. The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper

Mitochondrial Diseases

Mitochondria are crucial organelles for any cell type. Mitochondria take responsibility for not only energy production but also regulation of cell death, also called apoptosis; calcium storage; and heat production. Therefore, mitochondrial disease is implicated in the mode of action of many harmful factors for cells such as drugs and environmental contaminants, dysfunction of the oxygen transport system, malnutrition, intense exercise, and genetic variations. This book presents up-to-date knowledge about mitochondrial disease and its complex relation to some diseases such as cardiac failure, cancer, and Alzheimer's and Parkinson's diseases. This book will, therefore, be essential for readers who are interested in life sciences, especially in medicine

Djelovanje imidakloprida pod utjecajem piperonil butoksida i menadiona ovisno je o spolu, tkivu i trajanju izloženosti. I. dio - oksidativno i neurotoksično djelovanje

Earlier research has evidenced the oxidative and neurotoxic potential of imidacloprid, a neonicotinoid insecticide, in different animal species. The primary aim of this study was to determine how metabolic modulators piperonyl butoxide and menadione affect imidacloprid’s adverse action in the liver and kidney of Sprague-Dawley rats of both sexes. The animals were exposed to imidacloprid alone (170 mg kg-1) or in combination with piperonyl butoxide (100 mg kg-1) or menadione (25 mg kg-1) for 12 and 24 h. Their liver and kidney homogenates were analysed spectrophotometrically for glutathione peroxidase, glutathione S-transferase, catalase, total cholinesterase specific activities, total glutathione, total protein content, and lipid peroxidation levels. Imidacloprid displayed its prooxidative and neurotoxic effects predominantly in the kidney of male rats after 24 h of exposure. Our findings suggest that the observed differences in prooxidative and neurotoxic potential of imidacloprid could be related to differences in its metabolism between the sexes. Co-exposure (90-min pre-treatment) with piperonyl butoxide or menadione revealed tissue-specific effect of imidacloprid on total cholinesterase activity. Increased cholinesterase activity in the kidney could be an adaptive response to imidacloprid-induced oxidative stress. In the male rat liver, co-exposure with piperonyl butoxide or menadione exacerbated imidacloprid toxicity. In female rats, imidacloprid+menadione co-exposure caused prooxidative effects, while no such effects were observed with imidacloprid alone or menadione alone. In conclusion, sex-, tissue-, and duration-specific effects of imidacloprid are remarkable points in its toxicity.Rezultati ranijih istraživanja pokazali su oksidativni i neurotoksični potencijal imidakloprida, neonikotinoidnog insekticida, u različitih životinjskih vrsta. Primarni je cilj ovog istraživanja bio utvrditi kako modulatori metabolizma piperonil butoksid i menadion utječu na nepovoljne učinke imidakloprida na jetra i bubrege muških i ženskih štakora soja Sprague-Dawley. Životinje su 12 h odnosno 24 h bile izložene samo imidaklopridu (170 mg kg-1) ili njegovoj kombinaciji s piperonil butoksidom (100 mg kg-1) odnosno menadionom (25 mg kg-1). U homogenatima jetara i bubrega spektrofotometrijski su utvrđene razine glutation peroksidaze, glutation S-transferaze, katalaze, specifične aktivnosti ukupne kolinesteraze, ukupni glutation, ukupni proteini te razine lipidne peroksidacije. Imidakloprid se pokazao prooksidativnim i neurotoksičnim uglavnom u bubrezima muških štakora nakon 24-satne izloženosti. Naši rezultati upućuju na to da su razlike u prooksidativnom i neurotoksičnom djelovanju imidakloprida povezane sa spolnim razlikama. Predtretmanom piperonil butoksidom odnosno menadionom (90 min prije davanja imidakloprida) otkriveno je da imidakloprid djeluje na ukupnu aktivnost kolinesteraze specifično za pojedina tkiva. Povišena aktivnost kolinesteraza u bubrezima mogla bi odražavati prilagodbu na oksidativni stres uzrokovan imidaklopridom. Piperonil butoksid odnosno menadion u jetrima muških štakora samo su pogoršali toksičnost imidakloprida. U ženki je djelovanje imidakloprida s menadionom bilo prooksidativno; takvo se djelovanje nije vidjelo nakon primjene samo imidakloprida odnosno samo menadiona. Vjerujemo da je promjenjivo djelovanje imidakloprida s obzirom na spol, tkivo i trajanje izloženosti važno za daljnja istraživanja njegove toksičnosti