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The effectiveness of available neuropsychiatric drugs in the era of an increasing number of patients is not sufficient, and the complexity of neuropsychiatric disease entities that are difficult to diagnose and therapeutically is increasing. Also, discoveries about the pathophysiology of neuropsychiatric diseases are promising, including those initiating a new round of innovations in the role of oxidative stress in the etiology of neuropsychiatric diseases. Oxidative stress is highly related to mental disorders, in the treatment of which the most frequently used are first- and second-generation antipsychotics, mood stabilizers, and antidepressants. Literature reports on the effect of neuropsychiatric drugs on oxidative stress are divergent. They are starting with those proving their protective effect and ending with those confirming disturbances in the oxidation-reduction balance. The presented publication reviews the state of knowledge on the role of oxidative stress in the most frequently used therapies for neuropsychiatric diseases using first- and second-generation antipsychotic drugs, i.e., haloperidol, clozapine, risperidone, olanzapine, quetiapine, or aripiprazole, mood stabilizers: lithium, carbamazepine, valproic acid, oxcarbazepine, and antidepressants: citalopram, sertraline, and venlafaxine, along with a brief pharmacological characteristic, preclinical and clinical studies effects.

Background: We aimed to assess a liposomal fat-soluble vitamin formulation containing vitamin K2 with standard treatment in cystic fibrosis (CF)., Methods: A multi-center randomized controlled trial was carried out in 100 pancreatic-insufficient patients with CF. The liposomal formulation contained vitamin A as retinyl palmitate (2667 IU daily) and beta-carotene (1333 IU), D3 (4000 IU), E (150 IU), K1 (2 mg), and K2 as menaquinone-7 (400 µg). It was compared with the standard vitamin preparations in the closest possible doses (2500 IU, 1428 IU, 4000 IU, 150 IU, 2.14 mg, respectively; no vitamin K2) over 3 months., Results: Forty-two patients finished the trial in the liposomal and 49 in the control group (overall 91 pts: 22.6 ± 7.6 years, 62.6% female, BMI 19.9 ± 2.8 kg/m 2 , FEV1% 70% ± 30%). The main outcome was the change of vitamin status in the serum during the study (liposomal vs. standard): all-trans-retinol (+1.48 ± 95.9 vs. -43.1 ± 121.4 ng/mL, p = 0.054), 25-hydroxyvitamin D3 (+9.7 ± 13.4 vs. +2.0 ± 9.8 ng/mL, p = 0.004), α-tocopherol (+1.5 ± 2.5 vs. -0.2 ± 1.6 µg/mL, p < 0.001), %undercarboxylated osteocalcin (-17.2 ± 24.8% vs. -8.3 ± 18.5%, p = 0.061). The secondary outcome was the vitamin status at the trial end: all-trans-retinol (370.0 ± 116.5 vs. 323.1 ± 100.6 ng/mL, p = 0.045), 25-hydroxyvitamin D3 (43.2 ± 16.6 vs. 32.7 ± 11.5 ng/mL, p < 0.001), α-tocopherol (9.0 ± 3.1 vs. 7.7 ± 3.0 µg/mL, p = 0.037), %undercarboxylated osteocalcin (13.0 ± 11.2% vs. 22.7 ± 22.0%, p = 0.008)., Conclusion: The liposomal fat-soluble vitamin supplement containing vitamin K2 was superior to the standard form in delivering vitamin D3 and E in pancreatic-insufficient patients with CF. The supplement was also more effective in strengthening vitamin K-dependent carboxylation, and could improve vitamin A status.

Ethylene glycol (EG), in addition to its neurotoxic and nephrotoxic effects, evokes oxidative stress. The aim of this study was to assess the influence of the ethylene glycol on the biochemical indicators and oxidoreductive balance of patients treated for acute poisoning. The total study group consisted of 56 persons including 26 alcoholics who took EG as a substitute for ethyl alcohol in the course of alcohol dependence syndrome and 30 controls. Severity of poisoning, results of acid-base parameters, biochemical, and toxicological tests as well as biomarkers of the oxidative stress in blood were analyzed during the patients' hospitalization. The key issue was to assess the oxidative stress and biochemical disturbances caused by EG and the type of treatment applied in the course of poisoning. Significant changes in some parameters were found both at time of diagnosis and after treatment initiation (ethanol as an antidote and hemodialysis). The most important differences included the activity of hepatic parameters (aspartate aminotransferase, AST) and oxidative stress markers like catalase (CAT); correlation of the lipid peroxidation products level (TBARS) with urea concentration has been shown. On the last day of the hospitalization, in some cases, the mutual correlation between the evaluated markers were observed, for example, between alanine transaminase (ALT) and glutathione reductase (GR), and urea concentration and glutathione level (GSH/GSSG). The concentration of ions (H + ) had a major impact on the oxidoreductive balance, correlating with the elevated GR and GSH/GSSG levels.

Fat-soluble vitamin deficiency remains a challenge in cystic fibrosis (CF), chronic pancreatitis, and biliary atresia. Liposomes and cyclodextrins can enhance their bioavailability, thus this multi-center randomized placebo-controlled trial compared three-month supplementation of fat-soluble vitamins in the form of liposomes or cyclodextrins to medium-chain triglycerides (MCT) in pancreatic-insufficient CF patients. The daily doses were as follows: 2000 IU of retinyl palmitate, 4000 IU of vitamin D3, 200 IU of RRR-α-tocopherol, and 200 µg of vitamin K2 as menaquinone-7, with vitamin E given in soybean oil instead of liposomes. All participants received 4 mg of β-carotene and 1.07 mg of vitamin K1 to ensure compliance with the guidelines. The primary outcome was the change from the baseline of all-trans-retinol and 25-hydroxyvitamin D3 concentrations and the percentage of undercarboxylated osteocalcin. Out of 75 randomized patients ( n = 28 liposomes, n = 22 cyclodextrins, and n = 25 MCT), 67 completed the trial (89%; n = 26 liposomes, n = 18 cyclodextrins, and n = 23 MCT) and had a median age of 22 years (IQR 19-28), body mass index of 20.6 kg/m 2 [18.4-22.0], and forced expiratory volume in 1 s of 65% (44-84%). The liposomal formulation of vitamin A was associated with the improved evolution of serum all-trans-retinol compared to the control (median +1.7 ng/mL (IQR -44.3-86.1) vs. -38.8 ng/mL (-71.2-6.8), p = 0.028). Cyclodextrins enhanced the bioavailability of vitamin D3 (+9.0 ng/mL (1.0-17.0) vs. +3.0 ng/mL (-4.0-7.0), p = 0.012) and vitamin E (+4.34 µg/mL (0.33-6.52) vs. -0.34 µg/mL (-1.71-2.15), p = 0.010). Liposomes may augment the bioavailability of vitamin A and cyclodextrins may strengthen the supplementation of vitamins D3 and E relative to MCT in pancreatic-insufficient CF but further studies are required to assess liposomal vitamin E (German Clinical Trial Register number DRKS00014295, funded from EU and Norsa Pharma).

The review presents data from the last few years on bioanalytical methods used in therapeutic drug monitoring (TDM) of the 1st-3rd generation and the newest antiepileptic drug (AEDs) cenobamate in patients with various forms of seizures. Chemical classification, structure, mechanism of action, pharmacokinetic data and therapeutic ranges for total and free fractions and interactions were collected. The primary data on bioanalytical methods for AEDs determination included biological matrices, sample preparation, dried blood spot (DBS) analysis, column resolution, detection method, validation parameters, and clinical utility. In conclusion, the most frequently described method used in AED analysis is the LC-based technique (HPLC, UHPLC, USLC) combined with highly sensitive mass detection or fluorescence detection. However, less sensitive UV is also used. Capillary electrophoresis and gas chromatography have been rarely applied. Besides the precipitation of proteins or LLE, an automatic SPE is often a sample preparation method. Derivatization was also indicated to improve sensitivity and automate the analysis. The usefulness of the methods for TDM was also highlighted.

Toxic effects of ethylene glycol (EG) and its metabolites are mainly related to metabolic acidosis and kidney damage. EG biotransformation involving CYP2E1 affects the oxidant-antioxidant balance. The study assessed the effect of repeated administration of 4-methylpyrazole (4MP, 15mg/kg b.w. after 2h, followed by 10mg/kg b.w. every 12h) on renal function (creatinine, urea and urinary protein levels) as well as products of kidney's lipid peroxidation (MDA and TBARS levels) in rats poisoned with EG (5745mg/kg b.w.). Serum EG and glycolic acid (GA) concentrations were measured throughout the experiment. Repeated administration of 4MP reduced the rate of EG elimination, extended the period of EG persistence in serum and significantly limited formation of GA. The study showed the temporary intensification of kidney oxidative processes that correlated with changes in kidney function. It was found that the use of 4MP in EG poisoning inhibited its biotransformation to toxic metabolites, but simultaneously intensified oxidative damages in kidneys., (Copyright © 2017 Elsevier B.V. All rights reserved.)

The increasing availability of e-cigarettes is a potential toxicological concern. E-cigarettes appeared on the Polish market in 2006, and since 2009 they have been widely available with a new source of nicotine, the so-called e-liquid. In this paper two cases of suicidal oral and intravenous poisonings with the e-liquid are described. The clinical courses of these poisonings are presented. Nicotine and cotinine concentrations in the patient's blood were determined using high performance liquid chromatography with diode array detection. In the course of intoxication patient No. 1, classic symptoms of acute nicotine poisoning without convulsions were observed. Nicotine and cotinine concentrations measured in serum were 0.096 and 4.4mg/L, respectively. The case of patient No. 2, admission with no typical symptoms of nicotine poisoning was identified, except unconsciousness and slow respiration. Nicotine and cotinine concentrations in the serum at the time of No. 2 admissions were determined to be 0.8 and 1.3mg/L, respectively. With the increasing number of e-liquid poisonings cases, it should be aware that these products can be a readily available source of poison., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Context: In addition to designer benzodiazepines such as etizolam, deschloroetizolam, pyrazolam, diclazepam, nifoxipam, or clonazolam, a new psychoactive substance like flubromazolam, triazole of flubromazepam has become available. Flubromazolam is currently not marketed as a medication but rather as a research chemical and recreational drug. It mostly causes sedative effects but also has moderate anti-anxiety and muscle relaxant effects. A case of a severe intoxication of flubromazolam has been reported., Case Details: A 27-year-old man, presented with deep coma, bilateral pinpoint unreactive pupils, acute respiratory failure and hypotension, complicated by hypoxic ischemic changes in the central nervous system. A positive result of a urine screening test confirmed the presence of benzodiazepines, which resulted in administration of flumazenil and improved patient consciousness. Quantitative method of liquid chromatography indicated flubromazolam in the patient's serum at 59 ng/mL and urine at 105 ng/mL about 19 h after ingestion of 3 mg dose. On admission, serum creatine kinase was 15,960 U/L. The patient was treated with mechanical ventilation, intravenous fluids, flumazenil and continuous infusion of norepinephrine at a dose of 0.12 µg/kg/min. The patient survived and on the ninth day of hospitalization he was transferred to the Department of Neurology., Discussion: Flubromazolam is a new designer drug. Recreational use may be a cause of prolonged, severe intoxication associated with coma, hypotension, and rhabdomyolysis.

The post-injection olanzapine delirium/sedation syndrome (PDSS) was observed in a 60-year-old Caucasian, schizophrenic, non-smoker and underweight [body mass index (BMI), 18.2 kg/m(2) ] women after the fourth intramuscular injection of 405 mg olanzapine pamoate. Clinical symptoms of PDSS were similar to those of acute oral olanzapine intoxication. The patient received supportive treatment and recovered fully. High olanzapine concentrations in serum, with maximum level of 698 ng/mL, were confirmed by liquid chromatography with tandem mass spectrometry (LC-MS/MS). The authors wonder whether a low BMI and advanced age may predispose patients to PDSS occurrence., (© 2015 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).)

The consumption of energy beverages is increasing, especially among young people. The increasing consumption of these drinks increases the data of side effects. Case report: A 26-year old male was admitted to Toxicology Department suspected of intoxication due to ethyl alcohol and unknown psychoactive substances. The patient lost consciousness during a party in which he drank an unknown amount of ethyl alcohol mixed with an energy beverage ("Red Bull"). The patient and his friends strongly denied the use of psychoactive substances. On admission, the patient was stable, but unconscious (GCS 8 points), pupils wide, symmetric with weak reaction to light, respiratory rate 15/min. Neurological examination did not reveal any abnormalities. During the hospitalization, somnolence slowly disappeared and the patient became restless, with recurrent episodes of seizures not reacting to diazepam, clonazepam and midazolam infusion. The seizures finally abated after administration of barbiturates (Thiopental). This, in turn, caused respiratory insufficiency, requiring patient intubation and mechanical ventilation. The patients mental status and respiratory status slowly improved. After regaining consciousness, the patient strongly denied the use of psychoactive substances or of chronic alcohol use. He confirmed the single use of high, but not clearly defined, caffeine dosage (in the form of "Red Bull") mixed with alcohol. He mentioned that eight months earlier in similar circumstances he was admitted to the neurology department due to an episode of seizures. Ultimately the origin was not established, despite broad diagnostic testing. Thus the origin of the seizures was suggested to be of a toxicological origin. The patient was released home in good condition, without any side effects of the poisoning. The psychological examination doe not reveal any symptoms of alcohol or psychoactive substances addiction. In our case, due to the unclear nature of the history, we preformed broad diagnostic testing on admission to the hospital, which do not reveal the presence of any toxic substances except ethanol; concentration in the blood was 2,41 gil. Unfortunately, serum caffeine levels were not measured. There was no identification of any other factors that could be responsible for the observed symptoms. It appears that based on the interview, clinical manifestation, and negative toxicology laboratory testing (excluding the presence of ethanol), it is possible to connect the seizure state with the consumption of a high dose of energy drinks, rich in caffeine and taurine.

A serious case of barium intoxication from suicidal ingestion is reported. Oral barium chloride poisoning with hypokalemia, neuromuscular and cardiac toxicity, treated with intravenous potassium supplementation and hemodialysis, was confirmed by the determination of barium concentrations in gastric contents, blood, serum and urine using the inductively coupled plasma mass spectrometry method. Barium concentrations in the analyzed specimens were 20.45 µg/L in serum, 150 µg/L in blood, 10,500 µg/L in urine and 63,500 µg/L in gastric contents. Results were compared with barium levels obtained from a non-intoxicated person., (© The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: Severe metabolic acidosis is one of the most difficult diagnostic and therapeutic challenges. The most common causes of this type of acid-base balance disorder are toxic alcohols, e.g. methanol poisoning. Metabolites of methanol, formaldehyde and formic acid are responsible for severe symptoms of this poisoning., Objective: The aim of this study is a preliminary assessment of usefulness of formic acid detection by gas chromatography in the daily practice of clinical toxicology department in methanol poisoning confirmed by the designation of this alcohol in the blood., Methods: The study included 9 patients from Greater Poland region diagnosed with methanol poisoning. Blood samples were collected during routine laboratory tests, on admission secured at-80°C, and then formic acid was determined by head-space gas chromatography. The relationship between the concentration of blood formic acid and methanol, ethanol, and the acid-base balance parameters were evaluated., Results: The study group consisted of 9 men, aged 49.89 ± 6.17 years. All patients were diagnosed with alcohol dependence. In most cases (66.67%) and methanol poisoning occurred during ethanol abuse. The average blood methanol and ethanol concentrations were 2.48±1.74 g/L and 0.99±1.73 g/L respectively. The average blood formic acid concentration was 0.59±0.46 g/L, from 0.0 to 1.12 g/L. Acid-base balance parameters were (mean± SD): pH 7.00 ±0.36; pCO2 32.26 ± 14.54 mmHg; PO2 114.24±77.53 mmHg; BE -18.28 16.76 mmol/L; HCO3-12.70±11.53 mmol/L. There was a positive correlation be- tween the blood methanol and formic acid concentration. A negative correlation was found between the blood ethanol and formic acid concentration. In patients with positive blood ethanol concentration (1.74 to 5.0 g/L, mean 2.96±1.78 g/L) there was not any formic acid, despite the presence of methanol was confirmed. These patients did not demonstrate metabolic acidosis (mean±SD): pH 7.43 ±0.20; HCO3- 27.87 ± 2.36 mmol/L; BE 3.60 ±2.40 mmol/L. In contrast, in all patients with negative blood ethanol concentration, tests confirmed metabolic acidosis and elevated formic acid (mean SD): pH 6.80±0.20; HCO3- 5.12±1.67 mmol/L; BE-29.20±3.68 mmol/L; formic acid 0.89±0.16 g/L., Conclusion: Methanol poisoning cannot be confirmed by positive blood formic acid in patients with high blood ethanol concentration (≥1.74 g/L). In this kind of intoxication severe metabolic acidosis does not occur too. In patients with no detectable blood ethanol concentration, blood formic acid concentration can reach 1.12 g/L and correlates with the severity of metabolic acidosis.

Objectives: The aim of the study was to evaluate the influence of acetylsalicylic acid (ASA) on benzene hematotoxicity in rats., Materials and Methods: The study was carried out on rats exposed for 2, 4 and 8 weeks to benzene vapour at a concentration of 1.5 or 4.5 mmol/m(3) of air (5 days per week, 6 hours per day) alone or together with ASA at the doses of 5, 150 or 300 mg/kg body weight (per os)., Results: Benzene at a concentration of 4.5 mmol/m(3) caused a slight lymphopenia, granulocytosis and reticulocytosis in blood. In bone marrow traits of megaloblastic renewal, presence of undifferentiated cells and giant forms of granulocytes as well as an increase in myeloperoxidase and decrease in chloroacetate esterase activity and lipids content were noted. ASA (150 and 300 mg/kg b.w.) influenced some of hematological parameters, altered by benzene intoxication. ASA limited the solvent-induced alteration in blood reticulocyte count and in the case of bone marrow in the erythroblasts count. Traits of megaloblastic renewal in bone marrow were less pronounced. Besides, higher activity of myeloperoxidase and the decrease in the level of lipids in granulocytes were noted., Conclusion: Our results suggest that ASA limited the benzene-induced hematotoxicity.

Methoxetamine (MXE) is a novel synthetic drug, structurally related to phencyclidine, with ketamine-like properties. Available in Poland since 2010, with no legal control, is adverti. sed as the "ideal dissociation drug". The aim of this study was to present a case of nasal methoxetamine acute poisoning in a 28-year-old man, the course of treatment, and the method of identification of this substance in serum and urine. In the course of this intoxication extreme agitation and aggression with slight response to benzodiazepines were observed. The patient was confused, hallucinated. In addition, the physical examination re. vealed tachycardia 120/min and normal blood pressure (130/80 mm Hg). The period of acute poisoning was covered by amnesia. The MXE concentrations in serum and urine were determined using liquid chromatography-mass spectrometry (LC-MS-MS) method, and were respectively 270 ng/ml and 660 ng/ml. Confirmed MXE poisoning increases our knowledge about this new substance, providing relevant clinical and analytical data.

Objective: We report a case of abuse of weight-loss dietary supplement in 27-year-old man, with characteristic for amphetamine sympathomimetic symptoms and positive analysis of this drug in the urine by immunoassay method (FPIA; Axsym, Abbott). However positive result was not confirmed by liquid chromatography coupled with tandem mass spectrometry (LC-MS-MS)., Case Report: The patient ate nine tablets of the Thermal Pro with declared composition of caffeine (250 mg), bitter orange (200 mg), beta-phenylethylamine (100 mg), willow bark (75 mg), Cayenne pepper (40 mg), 1,3-dimethyloamyloamine (DMAA, 35 mg), gooseberry extract (20 mg), bergamot orange (20 mg), black pepper (5 mg), after two-month period of regular consumption at dose of 2-3 capsules per day. After 4 hours, during admission to the Department of Toxicology, patient manifested typical sympathomimetic symptoms: anxiety, agitation, pale skin, sweats, tachycardia 120/min, mydriasis. Following the outcome of detecting amphetamine/methamphetamine in the patient's urine at 2377 ng/mL concentration using FPIA method, drug intoxication was suspected. It was considered that the ingestion was intentional or unconscious of adulterated dietary supplement. In view of the strong opposition of the patient, who denied any use of psychoactive substances, it was decided to re-examine collected speciments. The liquid chromatography coupled to tandem mass spectrometry (LC-MS-MS) method did not confirm the presence of amphetamine in the patient's blood and urine. Based on the composition of dietary supplements for substances which could be responsible for the positive amphetamine result in urine by FPIA method and available literature data, it was concluded that the substances that may react in the immunoassay could be dimethylamyloamine (DMAA, geranamine) or bitter orange components., Conclusion: False positive urinalysis towards amphetamine/methamphetamine by immunoassay and presence of sympathomimetic effects may contribute to a false diagnosis of this drug poisoning. Definitive confirmation of such intoxication requires the use of the reference methods.

Background: The aim of the conducted studies was to evaluate the effect of 4-methylpyrazole, increasingly used in detoxifying treatments after ethylene glycol poisoning, on the activity of some antioxidant enzymes and lipid peroxidation formation in the liver of rats after experimental co-exposure to ethylene glycol and ethyl alcohol., Methods: The trials were conducted on adult male Wistar rats. Ethylene glycol (EG) at the dose of 3.83 g/kg bw and ethyl alcohol (EA) at the dose of 1 g/kg bw were administered po, and 4-methylpyrazole (4-MP) at the dose of 0.01 g/kg bw was administered ip. Parameters of antioxidant balance were evaluated in hepatic cytosol, including the activity of the following enzymes: glutathione S-transferase (GST), glutathione reductase (GR), glutathione peroxidase (GPx) and lipid peroxidation level (TBARS)., Results: The results suggest that evaluation of the effects of administrated 4-MP after co-exposure to EG and EA in the liver revealed statistically significant changes on antioxidant enzyme system and malondialdehyde formation., Conclusion: The changes in biomarkers activity indicate a greater production of free radicals which exceeds the capability of antioxidant system, appearing with oxidative stress in the group of animals treated by 4-MP combined with EG and EA.

Ethylene glycol (EG) is a multidirectional, dihydric alcohol, which is widely used in food, chemical and automotive industries. EG is a compound of similar toxicity to ethanol (EA). The EG biotransformation undergoes, mainly to glycolaldehyde and acids: glycolic, glyoxylic and oxalic acid, such metabolites, which exhibit strong narcotic effect on the central nervous system, causing profound metabolic acidosis and lead to severe nephropathy. Due to the wide availability of products containing ethylene glycol and its potential toxicity, in the case of the alcohol poisoning, the significant role in the diagnosis play: medical interview, observation of characteristic clinical symptoms, basic laboratory tests and detection of ethylene glycol in the biological material that confirm EG poisoning.

Cyanides are relatively rare cause of acute poisonings. The majority of data on toxic effects of cyanide compounds on the human body, come from the experiences gained from accidental poisonings in the workplace, with fire smokes or during chemical incidents. However, from immemorial time, cyanides were also used in suicide attempts. The aim of this paper is to present the case of suicidal cyanide poisoning of 26-year-old woman, who was admitted to the toxicology department one hour after ingestion of unknown cyanogenic compound, probably bought on the Internet. Despite intensive symptomatic treatment and antidote administration (hydroxocobalamine), patient died after 78 hours of treatment.

The aim of the study was to evaluate cytochrome P-450 dependent hepatic monooxygenases system and urinary excretions of phenol and muconic acid in animals subjected to acetylsalicylic acid (ASA) orally and benzene by inhalations. ASA increased urinary excretion of muconic acid although it did not affect the urinary level of phenol. Benzene decreased concentrations of P-450 and b(5) cytochromes and the activities of NADPH-cytochrome P-450 and NADH-cytochrome b(5) reductases. In rats exposed to ASA and benzene simultaneously the concentration of both cytochromes and the activity of the cytochrome dependent reductases was higher than in the rats exposed only to benzene and sometimes exceeded the control group values.

Adult male rats of Wistar strain were subcutaneously injected with a single dose of 0.025 mM CdCl2/kg body weight. The autopsies were performed 2 and 12 weeks post cadmium injection. Experimental animals showed a normal gain of body weight while a marked lowering of the testes weight was observed. The lowering of testes weight of cadmium treated rats occured mainly due to the necrosis of seminiferous tubules, volume of which is markedly lower if compared to intact control rats. After 2 weeks of experiment a marked enlargement of the interstitial gland of the testis occured while after 12 weeks the gland is markedly lower if compared to control rats and to rats studied 2 weeks post cadmium injection. Histochemical reactions for lactic, succinic, alpha-glycerophosphate and 3beta-hydroxy steroid dehydrogenases, NADH tetrazolium reductase, acid phosphatase and nonspecific esterases showed for irreversible necrotic changes of seminiferous tubules of cadmium treated rats while the damage to interstitial gland is only temporary.